Controlled Tumor Protein Research Articles

Blood TCTP as a biomarker associated with immunosuppressive features and resistance to immunotherapy in metastatic gastric cancer.

474 Background: Cancer biomarkers are essential for determining the prognosis of the disease and/or predicting its response to specific treatments. However, established biomarkers representing specific myeloid cell populations and representative biomarkers in gastric cancer remain unavailable. Therefore, this study aimed to explore the prognostic and immunological relevance of plasma translationally controlled tumor protein (TCTP) in patients with advanced gastric cancer treated with immune checkpoint inhibitor (ICI) and cytotoxic chemotherapy. Methods: Plasma samples were prospectively collected from the cohorts of patients with gastric cancer who were treated with 1 st line fluoropyrimidine plus platinum chemotherapy (n = 143, cohort 1) and 3 rd line nivolumab (n = 165, cohort 2). Plasma TCTP levels were quantified using ELISA, and multiplex proteomic analysis (Olink) was conducted to assess expression levels of immune-related proteins. An external single-cell RNA sequencing (scRNA-seq) dataset was employed to validate the findings. Results: Patients with high plasma TCTP levels (TCTP-high group) exhibited poor survival outcomes with 1 st line chemotherapy compared to those with low levels (TCTP-low group) in cohort 1. In the TCTP-high group, proteins associated with immunosuppressive myeloid cells, angiogenesis, and immune exclusion of T/NK cell function were upregulated, whereas proteins involved in T-cell activation/exhaustion were significantly upregulated in the TCTP-low group. The scRNA-seq analyses of myeloid cells revealed that TCTP pathway-associated genes (i.e., TLR2 , CXCL1, and CXCL2 ) were specifically expressed in immunosuppressive APOE + macrophages, THBS1 + macrophages, and CD1C + conventional type 2 dendritic cells. In the TCTP-high group, patients treated with nivolumab (cohort 2) also experienced poor survival outcomes. Conclusions: Plasma TCTP is a readily measurable prognostic biomarker, reflecting immunosuppressive signals of myeloid cells in patients with gastric cancer treated with ICI and chemotherapy.

Analyzing the functions of Translationally controlled tumor protein2 during growth, development and autophagy of Dictyostelium discoideum.

Translationally controlled tumor protein (TCTP) is a well conserved and ubiquitously expressed multifunctional protein found in many organisms and is involved in many pathophysiological processes like cell proliferation, differentiation, development and cell death. The role of TCTP in anti-apoptosis and cancer metastasis makes it a promising candidate for cancer therapy. Dictyostelium discoideum, a protist, has two isoforms (TCTP1 and TCTP2, now referred to as TPT1 and TPT2) of which we have earlier elucidated TPT1. Here, we analyzed the role of TPT2 in this organism. tpt2 transcript was present throughout growth and development and is localized in the prestalk/stalk regions of multicellular structures developed. tpt2 gene was disrupted with a BSR cassette using a double homologous recombination method. Disruption of tpt2 gene (tpt2‾) exhibit reduced cell proliferation and nutrient-uptake. Additionally, development in tpt2‾ was delayed by 2h, formed small-sized aggregates that developed into stalky fruiting bodies with reduced spore viability. In contrast, overexpressed tpt2 (tpt2OE) showed increased cell proliferation and development, formed large-size aggregates that developed into spory fruiting bodies with increased spore viability. TPT2 regulates prestalk/prespore ratio and cell-type differentiation as abrogation of tpt2 gene resulted in altered localization of cell-type markers and an inclination towards the prestalk/stalk pathway while tpt2OE showed a prespore/spore biasness when mixed with wild-type cells. Deletion of either tpt1 or tpt2 gene showed increased autophagic flux indicating their involvement in negative regulation of autophagy. This study provides insights into the intricate involvement of TCTP in cellular dynamics and development of D. discoideum.

Immunological Analysis of Prognostic Factors in Conversion Surgery Cases for Gastric Cancer.

In order to clarify the optimal strategy regarding conversion surgery (CS) for gastric cancer (GC) patients, we focused on clinicopathological findings, including immunological factors, related to the favorable prognosis in patients with stage IV GC who underwent CS. A total of 25 patients with Stage IV GC who underwent induction chemotherapy (IC) and CS at our hospital between 2010 and 2021 were enrolled in this study. Biopsy specimens before IC and surgical specimens were collected. Immunohistochemical staining was performed using programmed death-ligand 1 (PD-L1) antibody, translationally controlled tumor protein (TCTP) antibody, and CD20 antibody. Prognostic factors were investigated using clinicopathological factors as well as immunological factors such as PD-L1, TCTP, and CD20 expression. cN0, ycStage1-2, R0-1 surgery, D2 lymph node dissection, ypN0, and ypStage1-2 were significantly associated with favorable overall survival. Among patients who underwent R0/1 surgery, only histological type was a significant prognostic factor for recurrence-free survival. Low PD-L1 expression before IC and high TCTP expression after IC were significantly associated with favorable recurrence-free survival. In addition to clinical factors, high TCTP expression after IC was identified as a significant favorable prognostic factor, which could help in identifying candidates for CS in the future.

Translationally Controlled Tumor Protein Enhances Angiogenesis in Ovarian Tumors by Activating Vascular Endothelial Growth Factor Receptor 2 Signaling.

Translationally controlled tumor protein (TCTP) is a regulatory protein that plays pivotal roles in cellular processes including the cell cycle, apoptosis, microtubule stabilization, embryo development, stress responses, and cancer. However, the molecular mechanism by which it promotes tumor angiogenesis is still unclear. In this study, we explored the mechanisms underlying stimulation of angiogenesis by a novel TCTP. Recombinant TCTP enhanced vascular endothelial growth factor (VEGF)-induced endothelial cell migration, capillary-like tubular structure formation, and cell proliferation by interacting with VEGF receptor 2 (VEGFR-2) in vitro. In contrast, we showed that TCTP knockdown (using short interfering [si]TCTP) led to a decrease in ovarian tumor cells. We also examined the expression of VEGF and hypoxia inducible factor 1 (HIF-1α), an important angiogenic factor. The expression of VEGF as well as HIF-1α was dramatically decreased by siTCTP. Mechanistically, siTCTP inhibited VEGFR-2 tyrosine phosphorylation and phosphorylation of its downstream targets PI3K, Akt, and mTOR. Collectively, these findings indicate that TCTP can promote proliferation and angiogenesis via the VEGFR-2/PI3K and mTOR signaling pathways in ovarian tumor cells, providing new insight into the mechanism behind the involvement of TCTP in tumor angiogenesis.

Development of a molecular assay for the determination of Eimeria tenella oocyst viability.

Coccidiosis is caused by apicomplexan parasites of the genus Eimeria, which infect epithelial cells of the intestinal tract causing diarrhea and negatively impacting production in the poultry industry. The self-limiting and highly immunogenic nature of infection by Eimeria spp. make live vaccination an effective means of coccidiosis control. Paramount to vaccine efficacy is the ability to administer precise numbers of viable oocysts. Unfortunately, no rapid and accurate method for determination of oocyst viability is available presently. This study presents the development of a qPCR-based assay for assessment of Eimeria tenella Tyzzer, 1929 oocyst viability. Transcriptome sequencing supported identification of three viability assay target transcripts based on significant increase in abundance with heat-stimulation. Measurement of shifts in target abundances in response to heat stimulation in oocysts, that ranged from high viability to non-infectious, was achieved via qPCR. Omission of DNase treatment supported use of background DNA in RNA samples for normalization for parasite numbers and oocyst disruption efficiency, while spike in of exogenous RNA supported normalization for variations in RNA recovery and reverse transcription efficiency. The assay demonstrated strong correlation with oocyst viability as confirmed through live infection trials, showing the highest predictive value for a transcript encoding a putative partial translationally controlled tumor protein, XM_013379639.1. This assay provides results in hours and could reduce the reliance on time-consuming and expensive live-infection trials in oocyst viability testing and could improve the accessibility and efficacy of coccidiosis vaccines. Future iterations may facilitate multivalent vaccine quality control and environmental monitoring.

Effect of Stocking Density on Stress-Related Gene Expression of Pacific White Shrimp (Litopenaeus vannamei) Infected with Infectious Myonecrosis Virus (IMNV)

The stress level of vannamei shrimp (Litopenaeus vannamei) is affected by increased density and several genes are expressed under the condition. This study aimed to determine the expression of genes encoding white shrimp stress after density treatment and the infectious myonecrosis virus (IMNV) challenge test. A completely randomized design (CRD) was carried out with 6 treatment groups, i.e. 3 different stocking density groups without IMNV infection (100, 200, and 400 shrimp/m2) and 3 different stocking density groups + IMNV infection (100, 200, and 400 shrimp/m2). In addition, a shrimp density of 400 shrimp/m2 reported the fastest rate of developing the IMNV virus as seen from the clinical symptoms. The lowest cumulative number of shrimp deaths was at a density of 100 shrimp/m2 and was caused by the IMNV virus confirmed through RT-PCR. Expression of stress-coding genes was divided into upregulated and downregulated characteristics. The upregulated genes were lectin and translationally controlled tumor protein (TCTP), while the downregulated gene was Toll Receptor. The results showed that the expression of genes related to immunity in L. vannamei was upregulated after pathogen challenges such as lectin and TCTP, meanwhile, the Toll receptor gene was downregulated. Further study should also be performed to measure the expression of the three genes in revealing the immune pathways.

Screening and Functional Evaluation of Four Larix kaempferi Promoters.

Promoters are powerful tools for breeding new varieties using transgenic technology. However, the low and unstable expression of target genes is still a limiting factor in Larix kaempferi (Lamb.) Carr (Japanese larch) genetic transformation. In this study, we analyzed L. kaempferi transcriptome data, screened out highly expressed genes, cloned their promoters, and constructed plant expression vectors containing the β-glucuronidase (GUS) reporter gene driven by these promoters. Recombinant vectors were introduced into the L. kaempferi embryogenic callus by means of the Agrobacterium-mediated transient or stable genetic transformation method, and the promoter activity was then determined by measuring GUS expression and its enzyme activity in the transformed materials. Four highly expressed genes were identified: L. kaempferi Zhang Chen Yi-1 (LaZCY-1), Zhang Chen Yi-2 (LaZCY-2), Translationally Controlled Tumor Protein (LaTCTP), and ubiquitin (LaUBQ). The 2000 bp fragments upstream of ATG in these sequences were cloned as promoters and named pLaZCY-1, pLaZCY-2, pLaTCTP, and pLaUBQ. Semi-quantitative and quantitative RT-PCR analyses of transient genetic transformation materials showed that all four promoters could drive GUS expression, indicating that they have promoter activities. Semi-quantitative and quantitative RT-PCR analyses and the histochemical staining of stable genetic transformation materials showed that the pLaUBQ promoter had higher activity than the other three L. kaempferi promoters and the CaMV35S promoter. Thus, the pLaUBQ promoter was suggested to be used in larch genetic transformation.

Therapeutic efficacy of JEW-M449, an anti-TCTP monoclonal antibody, administered via the nasal route in a BALB/c mouse model of ovalbumin-induced acute asthma

Numerous studies have highlighted the role of translationally controlled tumor protein (TCTP) as a key inflammatory mediator of asthma and allergies. Our previous study revealed that blocking the cytokine-like activity of TCTP using JEW-M449, an anti-TCTP monoclonal antibody (mAb), alleviated allergic inflammation in asthmatic mice. This study aimed to determine whether directly delivering JEW-M449 into the respiratory tract is a more effective way of mitigating airway inflammation in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation than delivering this antibody via the intraperitoneal (IP) route. OVA-sensitized mice were intranasally administered JEW-M449 to enable its direct delivery to the respiratory tract before OVA challenge. We evaluated the changes in the levels of bronchoalveolar lavage fluid (BALF) cells, T helper type 2 (Th2) cytokines, OVA-specific immunoglobulin E (IgE), and histopathological alterations in the lung tissues. Intranasal (IN) administration of JEW-M449 significantly ameliorated the pathological changes associated with OVA-induced lung injury, including reduced inflammatory cell infiltration and mucus hypersecretion. Mice IN administered JEW-M449 also showed decreased OVA-mediated induction of Th2 cytokines in BALF and lung homogenates. Importantly, JEW-M449 delivered via the IN route reached the lung tissue more effectively and exerted superior anti-inflammatory effects in OVA-challenged mice than the IP-delivered JEW-M449. This study is the first to demonstrate the efficacy of directly delivering JEW-M449 anti-TCTP mAb into the respiratory tract to alleviate the asthma phenotype in a mouse model, thereby highlighting a potential delivery strategy for novel inhaled mAb therapeutics for human asthma.

Translationally controlled tumor protein interacts with TaCIPK23 to positively regulate wheat resistance to Puccinia triticina.

Hypersensitive response-programmed cell death (HR-PCD) regulated by Ca2+ signal is considered the major regulator of resistance against Puccinia triticina (Pt.) infection in wheat. In this study, the bread wheat variety Thatcher and its near-isogenic line with the leaf rust resistance locus Lr26 were infected with the Pt. race 260 to obtain the compatible and incompatible combinations, respectively. The expression of translationally controlled tumor protein (TaTCTP) was upregulated upon infection with Pt., through a Ca2+-dependent mechanism in the incompatible combination. The knockdown of TaTCTP markedly increased the area of dying cell and the number of Pt. haustorial mother cells (HMCs) at the infection sites, whereas plants overexpressing the gene exhibited enhanced resistance. The interaction between TaTCTP and calcineurin B-like protein-interacting protein kinase 23 (TaCIPK23) was also investigated, and the interaction was found occurred in the endoplasmic reticulum. TaCIPK23 phosphorylated TaTCTP in vitro. The expression of a phospho-mimic TaTCTP mutant in Nicotiana benthamiana promoted HR-like cell death. Silencing TaCIPK23 or TaCIPK23/TaTCTP co-silencing resulted in the same results as silencing TaTCTP. This suggested that TaTCTP is a novel phosphorylation target of TaCIPK23, and both participate in the resistance of wheat to Pt. in the same pathway.

Cucumber (Cucumis sativus L.) translationally controlled tumor protein interacts with CsRab11A and promotes activation of target of rapamycin in response to Podosphaera xanthii.

The target of rapamycin (TOR) kinase serves as a central regulator that integrates nutrient and energy signals to orchestrate cellular and organismal physiology in both animals and plants. Despite significant advancements having been made in understanding the molecular and cellular functions of plant TOR kinases, the upstream regulators that modulate TOR activity are not yet fully elucidated. In animals, the translationally controlled tumor protein (TCTP) is recognized as a key player in TOR signaling. This study reveals that two TCTP isoforms from Cucumis sativus, when introduced into Arabidopsis, are instrumental in balancing growth and defense mechanisms against the fungal pathogen Golovinomyces cichoracearum. We hypothesize that plant TCTPs act as upstream regulators of TOR in response to powdery mildew caused by Podosphaera xanthii in Cucumis. Our research further uncovers a stable interaction between CsTCTP and a small GTPase, CsRab11A. Transient transformation assays indicate that CsRab11A is involved in the defense against P. xanthii and promotes the activation of TOR signaling through CsTCTP. Moreover, our findings demonstrate that the critical role of TOR in plant disease resistance is contingent upon its regulated activity; pretreatment with a TOR inhibitor (AZD-8055) enhances cucumber plant resistance to P. xanthii, while pretreatment with a TOR activator (MHY-1485) increases susceptibility. These results suggest a sophisticated adaptive response mechanism in which upstream regulators, CsTCTP and CsRab11A, coordinate to modulate TOR function in response to P. xanthii, highlighting a novel aspect of plant-pathogen interactions.

TCTP regulates genotoxic stress and tumorigenicity via intercellular vesicular signaling

Oncogenic intercellular signaling is regulated by extracellular vesicles (EVs), but the underlying mechanisms remain mostly unclear. Since TCTP (translationally controlled tumor protein) is an EV component, we investigated whether it has a role in genotoxic stress signaling and malignant transformation. By generating a Tctp-inducible knockout mouse model (Tctp–/f–), we report that Tctp is required for genotoxic stress-induced apoptosis signaling via small EVs (sEVs). Human breast cancer cells knocked-down for TCTP show impaired spontaneous EV secretion, thereby reducing sEV-dependent malignant growth. Since Trp53–/– mice are prone to tumor formation, we derived tumor cells from Trp53–/–;Tctp–/f– double mutant mice and describe a drastic decrease in tumori-genicity with concomitant decrease in sEV secretion and content. Remarkably, Trp53–/–;Tctp–/f– mice show highly prolonged survival. Treatment of Trp53–/– mice with sertraline, which inhibits TCTP function, increases their survival. Mechanistically, TCTP binds DDX3, recruiting RNAs, including miRNAs, to sEVs. Our findings establish TCTP as an essential protagonist in the regulation of sEV-signaling in the context of apoptosis and tumorigenicity.

Exploiting the nematicidal compounds from guava endo microbiome against root-knot nematodes, Meloidogyneenterolobii

Guava root-knot nematode, Meloidogyne enterolobii has emerged as a major threat in tropical and sub-tropical countries across the globe. These nematodes utilize their esophageal gland-secreted protein, M. enterolobii Translationally Controlled Tumour Protein (MeTCTP) for successful parasitism on guava plants. Our current study was focused on identifying the biomolecules produced by nematicidal endophytic bacterial strains crucial for suppressing MeTCTP. Results of our study exhibited that among different isolates Bacillus cereus (GREB1) demonstrated superior nematicidal efficacy and biomolecules from this strain, such as 2,1,3-benzothiodiazole (−6.0 kcal/mol), 2 hexen-1-ol (−5.1 kcal/mol) and heptanoic acid (−4.5 kcal/mol), exhibited notable binding affinity to MeTCTP protein in docking studies. Molecular dynamics simulation studies underscored the stability, dynamics, and binding mechanisms of these biomolecules with MeTCTP. Furthermore, the results of the in vitro assay with identified biomolecules proved that 2,1,3 benzothiadiazole @ 200 ppm had 99% juvenile mortality. The probit analysis revealed the LC50 concentration of 2,1,3 benzothiadiazole (52.17 μg/mL), 2 hexen-1- ol (84.37 μg/mL) and heptanoic acid (141.93 μg/mL) respectively. Integrating in-silico and in-vitro bio-efficacy assays, our study provides a pivotal foundation for novel biomolecules against guava nematodes. Moreover, the study lays the foundation to formulate a novel solution comprising potent biomolecules to curb M. enterolobii populations, offering a promising avenue for effective crop protection.

Environmental-related doses of afidopyropen induced toxicity effects in earthworms (Eisenia fetida)

Afidopyropen has high activity against pests. However, it poses potential risks to the soil ecology after entering the environment. The toxicity of afidopyropen to earthworms (Eisenia fetida) was studied for the first time in this study. The results showed that afidopyropen had low level of acute toxicity to E. fetida. Under the stimulation of chronic toxicity, the increase of reactive oxygen species (ROS) level activated the antioxidant and detoxification system, which led to the increase of superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. Lipid peroxidation and DNA damage were characterized by the increase of malondialdehyde (MDA) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) contents. Meanwhile, the functional genes SOD, CAT, GST, heat shock protein 70 (HSP70), transcriptionally controlled tumor protein (TCTP), and annetocin (ANN) played a synergistic role in antioxidant defense. However, the comprehensive toxicity of high concentration still increased on the 28th day. In addition, strong histopathological damage in the body wall and intestine was observed, accompanied by weight loss, which indicated that afidopyropen inhibited the growth of E. fetida. The molecular docking revealed that afidopyrene combined with the surface structure of SOD and GST proteins, which made SOD and GST become sensitive biomarkers reflecting the toxicity of afidopyropen to E. fetida. Summing up, afidopyropen destroys the homeostasis of E. fetida through chronic toxic. These results provide theoretical data for evaluating the environmental risk of afidopyropen to soil ecosystem.

Targeting inhibition of TCTP could inhibit proliferation and induce apoptosis in AML cells

Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein, which participates in many important physiological processes. Recently, the roles of TCTP in cell proliferation and apoptosis, especially its close relationship with various tumors, have attracted widespread attention. In this study, we found that the protein level of TCTP was significantly reduced in acute promyelocytic leukemia cell line NB4 transfected with retinoic acid-induced gene G (RIG-G). The RIG-G was found in our previous work as a key mediator of anti-proliferative activity in retinoid/interferon-related pathways. Here, we tried to further explore the function of TCTP in the development of acute myeloid leukemia (AML) from different levels. Our results showed that inhibiting TCTP expression could attenuate AML cells proliferation and induce apoptosis both in AML cell lines and in xenograft of NOD-SCID mice. In addition, either compared with patients in complete remission or non-leukemia patients, we detected that the expression of TCTP was generally high in the fresh bone marrow of AML patients, suggesting that there was a certain correlation between TCTP and AML disease progression. Taken together, our study revealed the role of TCTP in AML development, and provided a potential target for AML treatment.

AI-based Virtual Screening of Traditional Chinese Medicine and the Discovery of Novel Inhibitors of TCTP.

Translationally controlled tumour protein (TCTP) is associated with tumor diseases, such as breast cancer, and its inhibitor can reduce the growth of tumor cells. Unfortunately, there is currently no effective medication available for treating TCTP-related breast cancer. The objective of this study was to explore the inhibitor candidates among natural compounds for the treatment of breast cancer related to TCTP protein. To explore the potential inhibitors of TCTP, we first screened out four potential inhibitors in the Traditional Chinese Medicine (TCM) for cancer based on AI virtual screening using the docking method, and then revealed the interaction mechanism of TCTP and four candidate inhibitors from TCM with molecular docking and molecular dynamics (MD) methods. Based on the conformational characteristics and the MD properties of the four leading compounds, we designed the new skeleton molecules with the AI method using MolAICal software. Our MD simulations have revealed that different small molecules bind to different sites of TCTP, but the flexible regions and the signaling pathways are almost the same, and the VDW and hydrophobic interactions are crucial in the interactions between TCTP and ligands. We have proposed the candidate inhibitor of TCTP. Our study has provided a potential new method for exploring inhibitors from Traditional Chinese Medicine (TCM).

A tryptophan-based assay method to search regulatory compounds for transcriptionally controlled tumor protein

Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find regulatory compounds. However, the molecular characteristics of TCTP made it difficult to search for chemicals interacting with it. In this study, a tryptophan-based assay method was designed and Y151W mutant TCTP was constructed to search binding chemicals. Since there is no tryptophan in the native sequence of TCTP, the incorporation of tryptophan in the Y151W mutant was very effective to establish the method. A flavonoid library was employed to the assay with the method. With the native and Y151W mutant TCTPs, three flavonoids such as morin, myricetin and isobavachalcone have been found to interact with TCTP. Combined with native gel electrophoresis, the binding region of isobavachalcone was suggested to be the flexible loop of TCTP. This approach can be easily applicable to find binding compounds of proteins with similar molecular characteristics of TCTP.

Potato virus Y viral protein 6K1 inhibits the interaction between defense proteins during virus infection.

14-3-3 proteins play vital roles in plant defense against various pathogen invasions. To date, how 14-3-3 affects virus infections in plants remains largely unclear. In this study, we found that Nicotiana benthamiana 14-3-3h interacts with TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (TCTP), a susceptibility factor of potato virus Y (PVY). Silencing of Nb14-3-3h facilitates PVY accumulation, whereas overexpression of Nb14-3-3h inhibits PVY replication. The antiviral activities of 3 Nb14-3-3h dimerization defective mutants are significantly decreased, indicating that dimerization of Nb14-3-3h is indispensable for restricting PVY infection. Our results also showed that the mutant Nb14-3-3hE16A, which is capable of dimerizing but not interacting with NbTCTP, has reduced anti-PVY activity; the mutant NbTCTPI65A, which is unable to interact with Nb14-3-3h, facilitates PVY replication compared with the wild-type NbTCTP, indicating that dimeric Nb14-3-3h restricts PVY infection by interacting with NbTCTP and preventing its proviral function. As a counter-defense, PVY 6K1 interferes with the interaction between Nb14-3-3h and NbTCTP by competitively binding to Nb14-3-3h and rescues NbTCTP to promote PVY infection. Our results provide insights into the arms race between plants and potyviruses.

Targeting the translationally controlled tumor protein by a monoclonal antibody improves allergic airway inflammation in mice

Secretion of translationally controlled tumor protein (TCTP) was found in body fluids during the late phase of allergic reactions, implicating TCTP in allergic diseases. Furthermore, blocking TCTP has been shown to be helpful in treating asthma and allergies in animal models. The objectives of this study were to produce anti-TCTP monoclonal antibodies (mAbs), test their ability to inhibit the cytokine-like function of dimeric TCTP (dTCTP) in vitro and to assess their therapeutic effects in a murine model of ovalbumin (OVA)-induced airway inflammation. We first verified the inhibitory effects of 4 anti-TCTP mAbs on dTCTP-induced secretion of IL-8 in BEAS-2B cells. To investigate the anti-inflammatory effect of anti-TCTP mAbs on allergic airway inflammation, we treated OVA-sensitized mice with anti-TCTP mAbs before OVA challenge. The changes in bronchoalveolar lavage fluid (BALF) cells, IL-4, IL-5, and IL-13 levels in both BALF and lung homogenates, plasma levels of OVA-specific IgE, and lung tissues were analyzed. We found that JEW-M449 anti-TCTP mAb bound to the flexible loop of TCTP and significantly inhibited dTCTP-induced IL-8 release, making it the most effective inhibitor in our study. We also found that treatment with JEW-M449 significantly reduced the infiltration of inflammatory cells and suppressed the OVA-induced upregulation of type 2 cytokines in both BALF and lung homogenates in a dose-dependent manner. In addition, JEW-M449 significantly attenuated the degree of goblet cell hyperplasia and mucus secretion. Our results demonstrate that specific targeting of the flexible loop of TCTP is a potent strategy for treating airway inflammatory diseases.

Elevated translationally controlled tumour protein promotes oral cancer progression and poor outcome.

Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1. TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression. TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells. Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers.

Long-Distance Movement of Solanum tuberosum Translationally Controlled Tumor Protein (StTCTP) mRNA.

Long-distance signaling molecules in plants, including different RNA species, play a crucial role in the development and environmental responses. Among these mobile signals, the Translationally Controlled Tumor Protein (TCTP) mRNA is one of the most abundant. TCTP regulates cell-cycle progression and programmed cell death and is involved in responses to abiotic and biotic stress as well as plant regeneration, among other functions. Considering that the ability to induce plant regeneration is linked to a possible role of TCTP in vegetative propagation and asexual reproduction, we analyzed TCTP overexpression in a solanaceous plant model that can reproduce asexually by regeneration from stolons and tubers. Therefore, in this study, the effect of transient expression of Solanum tuberosum TCTP (StTCTP) on tuber development and vegetative propagation was described. StTCTP mRNA was shown to be transported long-distance. Additionally, transient overexpression of StTCTP resulted in sprouts with a greater diameter compared to control plants. Furthermore, the early stages of tuberization were induced compared to control plants, in which only mature tubers were observed. These results suggest a role of TCTP in vegetative propagation and asexual reproduction.