Reciprocal Communication Research Articles

Promoting social competence and social inclusion in the preschool: a peer-based relational intervention

ABSTRACT Reviews concerning the enhancement of preschool children’s social competencies reveal areas within which teacher approach, definitions of social competence and methods of study can be enhanced. In response, teachers and researchers co-developed and introduced a peer-based relational intervention to support children’s communication, empathic response and non-homophilic choice of friendship/work mates. Within this design-based approach, a three-phase comparison was made in 14 English preschool classrooms. Results identified changes attributed to the intervention regarding: teacher behaviour (movement from giving directions to observation and support); child behaviour (enhanced reciprocal communication, empathic response to others and engagement in cognitively challenging activities) and an expansion of socially inclusive play/work mates. Not all teachers/classes responded to the relational approach in the same manner: those that engaged actively in the approach encouraged more social competence enhancements amongst children; those with lower engagement identified support/implementation problems and children showed less social competence advances.

Amalgam plays a dual role in controlling the number of leg muscle progenitors and regulating their interactions with the developing Drosophila tendon.

Formation of functional organs requires cell-cell communication between different cell lineages and failure in this communication can result in severe developmental defects. Hundreds of possible interacting pairs of proteins are known, but identifying the interacting partners that ensure a specific interaction between 2 given cell types remains challenging. Here, we use the Drosophila leg model and our cell type-specific transcriptomic data sets to uncover the molecular mediators of cell-cell communication between tendon and muscle precursors. Through the analysis of gene expression signatures of appendicular muscle and tendon precursor cells, we identify 2 candidates for early interactions between these 2 cell populations: Amalgam (Ama) encoding a secreted protein and Neurotactin (Nrt) known to encode a membrane-bound protein. Developmental expression and function analyses reveal that: (i) Ama is expressed in the leg myoblasts, whereas Nrt is expressed in adjacent tendon precursors; and (ii) in Ama and Nrt mutants, myoblast-tendon cell-cell association is lost, leading to tendon developmental defects. Furthermore, we demonstrate that Ama acts downstream of the FGFR pathway to maintain the myoblast population by promoting cell survival and proliferation in an Nrt-independent manner. Together, our data pinpoint Ama and Nrt as molecular actors ensuring early reciprocal communication between leg muscle and tendon precursors, a prerequisite for the coordinated development of the appendicular musculoskeletal system.

Meningkatkan Hasil Belajar Melalui Canva pada Materi Bersikap Kritis dan Bertanggungjawab Terhadap Media Massa dengan Model Problem Based Learning di Kelas X SMA Negeri 2 Temanggung

Learning is a process of implementing actions that involve interactions between teachers and students, along with reciprocal communication that occurs in the context of education to achieve learning goals. Manifested in government regulations, namely Government Regulation Number 57 of 2021 concerning National Education Standards which was amended by Government Regulation No. 4 of 2022, it is stated that process standards are minimum guidelines in implementing the education system in all regions subject to the laws of the Unitary State of the Republic of Indonesia. This is also reinforced by Permendikbud Ristek No. 16 of 2022 in Chapter I article 1 which discusses process standards. The article describes process standards referring to the minimum criteria of the learning process that apply to various paths, levels of education, and types with the aim of achieving graduate competency standards. The objectives of the study include (1) to determine how the implementation of the Problem Based Learning model improves student learning outcomes with the help of Canva on the material of being critical and responsible towards mass media in class X of SMA Negeri 2 Temanggung, (2) to determine the application of the use of Canva in exploring the learning outcomes of class X students of SMA Negeri 2 Temanggung on the material of being critical and responsible towards mass media. The type of research used is qualitative with a descriptive approach. Data collection techniques in this study used observation and tests. The data analysis techniques used consisted of data reduction by selecting raw data into information, data presentation, namely presenting data in the form of descriptions, graphs, tables and drawing conclusions by making conclusions from research results that refer to the formulation of the problem. The use of the Problem Based Learning model according to the syntax which includes student orientation to the problem, organizing students to learn, guiding individual and group investigations, developing and presenting results, analyzing and evaluating the problem-solving process, is effective in helping to improve learning outcomes and critical reasoning of students on the material of being critical and responsible towards mass media.

The Relationship between Peer Social Support and Homesickness Incidents in Overseas Students at the Faculty of Health Sciences, Muhammadiyah University, Jember

Overseas students are students who are studying outside their area of ​​origin. Some overseas students tend to experience homesickness because they miss their parents and hometown, so they need support from their environment. Social support is information and feedback from other people that shows that someone is loved and cared for, appreciated and respected and is involved in a network of reciprocal communication and obligations. Quantitative research with a cross-sectional approach. The population in this study were overseas students at the Muhammadiyah University of Jember, Faculty of Health Sciences Class of 2023. The population in this study was 53 overseas students with a sample size of 47 people and was taken using simple random sampling techniques. The statistical test between peer support and the incidence of homesickness as measured using Spearman rho with α = 0.05 resulted in p value = 0.000, and r = -0.625, meaning that there is a relationship between social support from peers and the incidence of homesickness in overseas students. The suggestion of this research is that health institutions are advised to provide education related to social support from peers, especially overseas students, so that they are able to adapt to new environments.

Neural Circuitries between the Brain and Peripheral Solid Tumors.

The recent discovery of the pivotal role of central nervous system (CNS) in controlling tumor initiation and progression has opened a new field of research. Increasing evidence suggests a bidirectional interaction between the brain and tumors. The brain influences the biological behavior of tumor cells through complex neural networks involving the peripheral nervous system, the endocrine system, and the immune system, while tumors can establish local autonomic and sensory neural networks to transmit signals into the CNS, thereby affecting brain activity. This review aims to summarize the latest research in brain-tumor crosstalk, exploring neural circuitries between the brain and various peripheral solid tumors, analyzing the roles in tumor development and the related molecular mediators and pathological mechanisms, and highlighting the critical impact on the understanding of cancer biology. Enhanced understanding of reciprocal communication between the brain and tumors will establish a solid theoretical basis for further research and could open avenues for repurposing psychiatric interventions in cancer treatment.

Spatiotemporally distinct roles of cyclooxygenase-1 and cyclooxygenase-2 at fetomaternal interface in mice.

Embryo implantation is crucial for ensuring a successful pregnancy outcome and subsequent child health. The intrauterine environment during the peri-implantation period shows drastic changes in gene expression and cellular metabolism in response to hormonal stimuli and reciprocal communication with embryos. Here, we performed spatial transcriptomic analysis to elucidate the mechanisms underlying embryo implantation. Transcriptome data revealed that lipid metabolism pathways, especially arachidonic acid-related (AA-related) ones, were enriched in the embryo-receptive luminal epithelia. Cyclooxygenases (COXs), rate-limiting enzymes involved in prostaglandin production by AA, were spatiotemporally regulated in the vicinity of embryos during implantation, but the role of each COX isozyme in the uterus for successful pregnancy was unclear. We established uterine-specific COX2-knockout (uKO) and COX1/uterine COX2-double-KO (COX1/COX2-DKO) mice. COX2 uKO caused deferred implantation with failed trophoblast invasion, resulting in subfertility with reduced pregnancy rates and litter sizes. COX1/COX2 DKO induced complete infertility, owing to abrogated embryo attachment. These results demonstrate that both isozymes have distinct roles during embryo implantation. Spatial transcriptome and lipidome analyses revealed unique profiles of prostaglandin synthesis by each COX isozyme and spatiotemporal expression patterns of downstream receptors throughout the endometrium. Our findings reveal previously unappreciated roles of COXs at the fetomaternal interface to establish early pregnancy.

Neurological Validation of ASD Diagnostic Criteria Using Frontal Alpha and Theta Asymmetry.

Background/Objectives: Diagnosis of Autism Spectrum Disorder (ASD) relies on the observation of difficulties in social communication and interaction, plus the presence of repetitive and restrictive behaviors. The identification of neurological correlates of these symptoms remains a high priority for clinical research, and has the potential to increase the validity of diagnosis of ASD as well as provide greater understanding of how the autistic brain functions. This study focused on two neurological phenomena that have been previously associated with psychiatric disorders (alpha- and theta-wave asymmetry across the frontal region of the brain), and tested for their association with the major diagnostic criteria for ASD. Methods: A total of 41 male autistic youth underwent assessment with the Autism Diagnostic Observation Schedule (ADOS-2) and 3 min of eyes-closed resting EEG to collect alpha- and theta-wave data from right and left frontal brain sites. Results: Different associations were found for theta versus alpha asymmetry and the ADOS-2 subscales, across different brain regions responsible for a varying range of cognitive functions. In general, theta asymmetry was associated with conversation with others, sharing of enjoyment, and making social overtures, whereas alpha asymmetry was linked with making eye contact, reporting events to others, and engaging in reciprocal social communication. Specific brain regions involved are identified, as well as implications for clinical practice. Conclusions: Specific autism symptoms may be associated with selected brain region activity, providing a neurological basis for diagnosis and treatment.

The Role of Public Relations and the Positive Image of Regional Owned Enterprises (BUMD)

Public relations is a party that can connect a company with the community to create reciprocal communication and establish good relationships. This research aims to determine how BUMDs carry out their public relations role and create a positive image for the company. This research uses a qualitative descriptive analysis method. Interviews, observation, and documentation were carried out using data collection methods. The theory used in this research is the Role Theory of Public Relations. The research results show that the role of Regional Drinking Water Company (PDAM) Tirtajati Public Relations is to provide comfort, understanding, information, and solutions to customers. Public Relations of PDAM Tirtajati collects aspirations and complaints and then connects them to related fields. Several inhibiting factors, such as insufficient services, impacted the community's negative response. Public Relations of PDAM Tirtajati strives to provide excellent service, establishes good communication with customers, provides complaint services via WhatsApp Center and Social Media to make it easier for the public, and establishes external communication with other agencies or organizations, public relations also provide explanation of the problems that occur, then offers solutions and treatments to resolve issues.

Development of a standardized set of outcomes for autism spectrum disorder: The International Consortium for Health Outcomes Measurement (ICHOM)

BackgroundAutism spectrum disorder (ASD) is characterized by persistent deficits in reciprocal social interaction, communication, and restricted, repetitive, behaviour, that are atypical or excessive for the individual’s age and sociocultural context (Diagnostic and Statistical Manual 5th ed TR.; 2022). The rate of ASD continues to increase and remains a concern due to inequitable access to diagnosis and quality services. A lack of standardization in assessment and treatment presents further difficulty in benchmarking and improving care. MethodThe International Consortium for Health Outcomes Measurement (ICHOM) recruited a Working Group (WG) of 20 subject matter experts, including researchers, clinicians, policy makers, and lived-experience experts to identify a minimum set of measurable outcomes along with case mix variables (i.e., risk adjustment factors). A proposed set of Patient Centered Outcome Measures (henceforth known as the ASD Set) was identified and endorsed using a modified Delphi process to reach consensus. ResultsThe WG took into consideration variation in global health, social care and educational systems were considered to ensure implementation of the ASD Set is feasible. The Set includes a core set of measurable outcomes (i.e., domains) that include core symptoms, daily functioning, accessibility, and support. ConclusionsThe ICHOM ASD Set is a scientifically-sound, internationally vetted tool that will enable assessment of care for individuals with ASD that can facilitate targeted, person-centered clinical and social inclusion strategies. Large scale implementation and use should generate standardized data describing the individual's health and wellbeing that can inform decision-making, quality improvement and best-practices insights.

Hypermetabolic state is associated with circadian rhythm disruption in mouse and human cancer cells

Crosstalk between metabolism and circadian rhythms is a fundamental building block of multicellular life, and disruption of this reciprocal communication could be relevant to disease. Here, we investigated whether maintenance of circadian rhythms depends on specific metabolic pathways, particularly in the context of cancer. We found that in adult mouse fibroblasts, ATP levels were a major contributor to signal from a clock gene luciferase reporter, although not necessarily to the strength of circadian cycling. In contrast, we identified significant metabolic control of circadian function across a series of pancreatic adenocarcinoma cell lines. Metabolic profiling of congenic tumor cell clones revealed substantial diversity among these lines that we used to identify clones to generate circadian reporter lines. We observed diverse circadian profiles among these lines that varied with their metabolic phenotype: The most hypometabolic line [exhibiting low levels of oxidative phosphorylation (OxPhos) and glycolysis] had the strongest rhythms, while the most hypermetabolic line had the weakest rhythms. Pharmacological enhancement of OxPhos decreased the amplitude of circadian oscillation in a subset of tumor cell lines. Strikingly, inhibition of OxPhos enhanced circadian rhythms only in the tumor cell line in which glycolysis was also low, thereby establishing a hypometabolic state. We further analyzed metabolic and circadian phenotypes across a panel of human patient-derived melanoma cell lines and observed a significant negative association between metabolic activity and circadian cycling strength. Together, these findings suggest that metabolic heterogeneity in cancer directly contributes to circadian function and that high levels of glycolysis or OxPhos independently disrupt circadian rhythms in these cells.

Circadian rhythms of antioxidant enzymes activity, clock, and inflammation factors are disrupted in the prefrontal cortex of aged rats. Potential targets for therapeutic strategies for a healthy aging.

Age impairs cognitive functions and antioxidant defenses, for example, by increasing oxidative stress and inflammation in the brain. However, so far, there is no report on the consequences of aging on temporal patterns of proteins and lipids oxidation, antioxidant enzymes activity, endogenous clock and proinflammatory cytokine, in the prefrontal cortex (PFC). Therefore, our objectives here were: 1) to investigate the endogenous nature of 24h-rhythms of lipoperoxidation, protein carbonyls levels, CAT and GPx activity, RORa, and TNFα, in the rat PFC, and 2) to study the consequences of aging on the circadian organization of those factors in the same brain area. To do that, 3- and 22-mo-old male Holtzman rats were maintained under constant darkness conditions during 15 days before reaching the corresponding age. PFC samples were isolated every 4 h, under dim-red light, during a 24h period. Our results revealed circadian patterns of antioxidant enzymes activity, oxidative stress, RORa and TNFα proteins levels, in the PFC of young rats. The circadian distribution of the rhythms’ phases suggests the existence of a reciprocal communication among the antioxidant defenses, the endogenous clock, and the inflammation, in the PFC. Noteworthy, such circadian organization disappears in the PFC of aged rats. An increased oxidative stress would make the redox environment to change into an oxidative status, which alters the endogenous clock activity and disrupts the circadian organization of, at least part, of the antioxidant defenses and the TNFα, in the PFC. These results might highlight novel chronobiological targets for the design of therapeutic strategies addressed to a healthy aging.

Enhancing Student Success in Higher Education: A Human-Centered Design Thinking Approach

Higher education institutions increasingly recognize the need to revolutionize approaches to student success. This study employs Human-Centered Design Thinking (HCDT), addressing the challenges faced by students and developing initiatives aimed at improving retention, progression, and graduation rates. Approximately 90 undergraduate students participated in the HCDT sessions, sharing insights about their academic progress. Through a collaborative process, students innovatively designed strategies to overcome these challenges. The HCDT process produced four key themes: proper and timely advisement; courses, schedules, and majors responsive to student demand; reciprocal communication clarity within and about courses; and resource knowledge availability and access. This study features the transformative potential of HCDT in higher education, placing students at the forefront of understanding challenges and designing strategies. By embracing this human-centered approach, institutions can significantly enhance retention, progression, and graduation rates, contributing to an inclusive and supportive educational environment.

Internalisasi Karakter Islami Berbasis Projek Penguatan Profil Pelajar Pancasila (P5) di SMP Plus Al-Kautsar Malang

The current moral degradation in the country illustrates the significance of character educatian. The purposed of this study was to examine how students at SMP Plus Al-Kautsar Malang internalize the values of the Pancasila students profile in order to develop Islamic character. The research focuses on the outcomes of the internalization of Pancasila student profile values in the development of Islamic character, along with a number of elements that facilitate and hinder this process. Descriptive qualitative methodology was employed in this study, along with methods for gatering data that included documentasion, interview, and observation. The findings of the study demonstraded that there were three primary phases in the process by which students at SMP Plus Al-Kautsar Malang internalized the significance of the Pancasila student profile in shaping their Islamic character. The first stage is value transformation, which involves distributing good moral values by providing direction and advice regarding good and bad values. The second stage is value transaction, which involves reciprocal communication between educators and students to ensure understanding of values. The third stage is the transinternalization of values, which involves habituation, Islamic activities, and project-based learning (P5). The strategies implemented include habituation, example, monitoring, and giving rewards and punishments. The results of the study show the strong influence that students have at SMP Plus Al-Kautsar Malang when internalizing the importance of the Pancasila student profile in shaping Islamic character. The students have succeeded in forming answers, independent, religious, and socially conscious.

OTHR-23. PATIENT DESIRE TO SHARE DATA AND PARTICIPATE IN RESEARCH IN THE DIPG/DMG COMMUNITY

Abstract Direct and reciprocal communication between patient communities and their research and care teams is essential to building trust and ensuring that all essential information is shared. Patient participation in data collection of any sort is often challenging, as patients may be hesitant or unmotivated to share their information. The DIPG/DMG patient community faces the opposite challenge. Because of the frustration of the lack of treatment options and the established trust that exists between patient families and research professionals, DIPG/DMG patient families are both willing and eager to share any information they can. Patient families have seen how their knowledge has helped other families navigate impossible situations and care teams understand how to better support their patients. The information families eagerly provide is crucial to advancing treatment and research. Patient families have repeatedly expressed willingness to participate in quality of life assessments, repeated surveys during and after treatment, and provide their medical and biological information in the hopes that it can aid research. There is a need for a centralized manner for all of this data to be shared by the patient and accessed by care teams and researchers. Patient-led initiatives are addressing this by creating a network of resources. This network helps to guide other patient families through the data-sharing process, address concerns, and find ways to provide what is needed to push research and treatments ahead. There are many benefits to having a centralized data ecosystem for researchers and care teams, such as standardizing data collection and ease of analysis. In the future, this centralized hub could inform personalized care, making options such as n-of-1 trials and matching patients to optimal clinical trials possible in a manner that is effective and efficient.

Patient participation in orthopaedic care—a survey on hip surgery patients’ preferences for and experiences of engagement in their health and healthcare

IntroductionQuality in health services is increasingly associated with enabling patients to participate in their own health and healthcare by recognising their resources and needs. Despite a growing recognition as to whether such participation is enabled, little is known regarding opportunities for preference-based patient participation in orthopaedic care. AimsTo investigate preference-based participation for patients in orthopaedic care due to hip surgery. MethodsPatients across 17 Swedish orthopaedic units who had had hip surgery, due to hip fracture or osteoarthritis, January–April 2021 were invited to complete the validated 4Ps questionnaire. Of 1514 patients, 458 patients returned the questionnaire with reports on their preferences for and experiences of participation. Each of the 4Ps’ 12 items were analysed separately using descriptive and comparative statistics. ResultsA complete match in preferences for, and experiences of, participation was achieved with variation between items for 41%–50% of the patients; if almost matches were included, this occurred for 57%–77% of the patients. Less participation than preferred was most common in terms of having had reciprocal communication, opportunities for partaking in planning, and in learning how to manage symptoms/issues. Hip fracture surgery was significantly associated with experiencing lower levels of participation than preferred. ConclusionThough standardised care promotes efficient hip surgery care, our study suggests a need for more person-centred opportunities to engage. A discrepancy was noted between patients’ resources and preparation for their participation in and beyond the hip surgery process, particularly for self-care activities, calling for better use of nursing resources. IdNCT04700969 with the U.S National Institutes of Health Clinical Registry.

Māori and Pacific families’ experiences and perspectives of cardiovascular care; A qualitative study

ObjectiveThis study aimed to understand the reasons behind evidence-practice gaps and inequities in cardiovascular care for Māori and Pacific people, as evidenced by the experiences and perspectives of patients and their families. MethodsThe research was guided by Māori and Pacific worldviews, incorporating Kaupapa Māori Theory and Pacific conceptual frameworks and research methodologies. Template analysis was used to analyse interview data from 61 Māori and Pacific people who had experienced a cardiovascular disease (CVD) risk assessment, acute coronary syndrome, and/or heart failure. ResultsThe range of experiences relating to participants’ heart health journeys are presented in five main themes: Context, Mana (maintaining control and dignity), Condition, People and Journey. ConclusionsMāori and Pacific people want to take charge of their heart health but face challenges. Participants described important obligations to family, community and tikanga (the culturally correct way of doing things). Participants described times when health care undermined existing responsibilities, their dignity and/or their mana, and they felt excluded from treatment as a result. Implications for Public HealthGood reciprocal communication, stemming from a high-quality relationship is essential for successful outcomes. A workforce that is representative of the population it serves and is culturally safe lays the foundation for excellence in care.

Development Model of Augmented Reality: A Need Analysis of Vocabulary Book for ESP Students

Abstract. The real challenge in 5.0 society requires meeting the needs of future generations who can use foreign languages and master technology. This study investigated the need for specific learning sources or materials for vocational students specifically majoring in Informatics Engineering in vocabulary learning. Since vocabulary is a fundamental language aspect of using English in reciprocal communications, this study is a type of survey research that uses quantitative and qualitative data analysis techniques. The instruments used to obtain the data were developed referring to the principal notion of a need assessment proposed by Hutchinson and Waters, validated by a language expert, and served through a questionnaire. The setting of this study involved 48 students of Vocational Students of Informatics Engineering at a private vocational school in Jakarta, Indonesia. The results showed that students of Informatics Engineering at vocational schools must be able to communicate in English, both written and spoken, using the specific term related to their department. Besides studying ESP to work, some students planned to continue to higher education with expertise in linear education. Therefore, they need to learn vocabulary with the integration of technology as they are supposed to deal with it in their field of work in informatics engineering to join the 5.0 society with the advancement of augmented reality-based media. Keywords: Technology, Augmented Reality, Vocabulary, English for Specific Purposes, Vocational School

Gaya Komunikasi Sutradara dalam Mengarahkan Pemain dalam Film Turah

The director's communication style is an important element in the process of directing players according to the script and storyline of a film. This paper aims to describe the director's communication style in the pre-production and production stages. This paper uses a descriptive qualitative approach with data collection techniques by interviewing the director and Turah's cast. The results of the study found that the director of the Turah film, Wicaksono Wisnu Legowo, used a communication style that dynamic which means that at each stage of film production, the director uses a different style. In the pre-production stage the director uses a reciprocal communication style in the preparatory sessions with the actors and a freelance communication style in the rehearsal sessions while in the production stage of the mise en scene sessions and directing the actors, the director uses a structured communication style and a dynamic communication style in the pre-take preparation sessions.

Abstract PO3-24-12: CRIPTO-regulated extracellular vesicles mediate heterotypic cellular crosstalk in triple negative breast cancers

Abstract Tumor progression involves the dynamic interaction between various cell types within the tumor microenvironment. Fibroblasts, which normally participate in wound healing, exhibit reciprocal communication with breast cancer cells that contributes to tumor cell plasticity and heterogeneity. Gaining insights into the molecular mechanisms underlying cell-to-cell communication, which drive cellular plasticity and play a pivotal role in breast cancer progression and metastasis, has the potential to unlock novel avenues for targeted therapeutic interventions. The small GPI-adaptor protein CRIPTO is a key player in this context. CRIPTO orchestrates the activity of TGF-β and growth factor-like signaling pathways that activate c-Src/MEK/AKT. CRIPTO is expressed during mammary development, wound healing, and breast cancer but is largely undetectable in homeostatic tissue, making it a promising therapeutic target. Our previous studies have demonstrated that the activity of CRIPTO is contingent upon cellular stress, with pronounced influence within pro-fibrotic, hypoxic domains of tumors. Importantly, we have shown that inhibition of CRIPTO using the soluble recombinant protein antagonist A4Fc effectively impedes the progression of triple negative breast cancer (TNBC) in murine xenograft models. Building upon these findings, we have been dissecting CRIPTO‘s role in coordinating fibroblast activation and cell-state reprogramming in TNBC. Notably, we have found that inhibition of CRIPTO with A4Fc suppresses cancer associated fibroblast (CAF) activation and collagen remodeling in vivo. And, by modeling tumor cell:fibroblast crosstalk using in vitro organoid co-cultures, we have demonstrated CRIPTO expression in tumor cells is necessary for extracellular vesicle (EV) uptake by fibroblasts, their SMAD pathway activation and their priming for reciprocal signaling back to tumor cells to for transcriptional reprogramming and cellular invasion. The significance of these findings lies in their potential to pave the way for the development of new therapies specifically targeting crucial tumor cell:fibroblast crosstalk mechanisms at primary and metastatic sites. Plasticity targeting therapies are urgently needed in the treatment of TNBC and other malignancies, and hold great promise for improving patient outcomes. Citation Format: David Freeman, Benjamin Spike, Brooke Gates. CRIPTO-regulated extracellular vesicles mediate heterotypic cellular crosstalk in triple negative breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-24-12.

Abstract LB319: Klf5 acetylation remodels tumor microenvironment to constrain PTEN-deficient prostate tumor growth

Abstract Prostate cancer is the most common cancer and the second leading cause of cancer-related death in men in the United States. PTEN deficiency is prevalent in patients with prostate cancer. As a tumor suppressor, PTEN is mutated in approximately 20% of primary prostate cancers, and up to 50% of metastatic castration resistant prostate cancer. PTEN inactivation results in high-grade adenocarcinoma with a long latency. The limited tumor progression induced by PTEN deficiency suggests that additional molecular events are activated to constrain tumor progression, and second hits are required. Understanding these secondary genetic hits will provide the rationale for combined therapies in prostate cancer treatment. In this study, we employed a unique genetically knockin mouse model and found that PTEN deficiency induces a KLF5 K369 acetylation-dependent barrier that attenuates FGFR1 signaling and constrains prostate tumor growth. More importantly, we discovered novel microenvironmental crosstalk between prostate cancer cells and cancer associated fibroblasts (CAFs). As suggested by RNA-seq and bioinformatic analyses and further validated by molecular and cellular experiments, we found that interruption of KLF5 acetylation in cancer cells stimulates CAFs to release FGF9 via TNF-α, and FGF9 activating FGFR1 signaling in cancer cells. In addition to this paracrine crosstalk, deacetylated KLF5 induces CX3CR1 and facilitates FGFR1 activation. Our findings provide a proof of concept for posttranslational modifications as essential molecular events induced by PTEN inactivation to stall prostate cancer progression and demonstrate KLF5 acetylation as a key component in a negative feedback loop by which FGFR1 was suppressed by AKT activation. This study reveals a paracrine reciprocal communication between cancer cells and fibroblasts and provides a clinical rationale for combined therapies using FGFR1 inhibitors (or CX3CR1 inhibitors) and p-AKT inhibitors in PTEN-deficient prostate cancer. Citation Format: Baotong Zhang, Mingcheng Liu, Fengyi Mai, Siyuan Xia, Jin-Tang Dong. Klf5 acetylation remodels tumor microenvironment to constrain PTEN-deficient prostate tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB319.