Metastasis Of Various Types Research Articles

The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity

Rosmarinic acid (RA), a polyphenolic compound found in herbs, such as rosemary, basil, and mint, has garnered significant attention due to its potent antioxidant and anticancer properties. This review examined the molecular mechanisms underlying these properties and their potential application in cancer prevention and therapy. It focuses specifically on RA’s role in modulating cancer-related pathways and presents a detailed analysis of recent advancements in this area. A systematic review of PubMed, Scopus, and Web of Science databases was conducted in accordance with PRISMA (Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, focusing on studies published between 2019 and 2024. A total of 25 articles providing evidence from in vitro, in vivo, and in silico studies were selected. These findings elucidate the role of RA in inhibiting tumor cell proliferation, inducing apoptosis, and preventing metastasis in various types of cancer through diverse mechanisms, including its antioxidant properties. Despite these promising results, RA’s bioavailability challenges limit its therapeutic efficacy, underscoring the necessity for improved delivery methods. This review concludes that RA exhibits significant potential as a natural agent for cancer prevention and treatment, although further clinical trials are warranted.

The possible correlation between miR-762, Hippo signaling pathway, TWIST1, and SMAD3 in lung cancer and chronic inflammatory diseases

MicroRNAs are small RNA molecules that have a significant role in translational repression and gene silencing through binding to downstream target mRNAs. MiR-762 can stimulate the proliferation and metastasis of various types of cancer. Hippo pathway is one of the pathways that regulate tissue development and carcinogenesis. Dysregulation of this pathway plays a vital role in the progression of cancer. This study aimed to evaluate the possible correlation between miR-762, the Hippo signaling pathway, TWIST1, and SMAD3 in patients with lung cancer, as well as patients with chronic inflammatory diseases. The relative expression of miR-762, MST1, LATS2, YAP, TWIST1, and SMAD3 was determined in 50 lung cancer patients, 30 patients with chronic inflammatory diseases, and 20 healthy volunteers by real-time PCR. The levels of YAP protein and neuron-specific enolase were estimated by ELISA and electrochemiluminescence immunoassay, respectively. Compared to the control group, miR-762, YAP, TWIST1, and SMAD3 expression were significantly upregulated in lung cancer patients and chronic inflammatory patients, except SMAD3 was significantly downregulated in chronic inflammatory patients. MST1, LATS2, and YAP protein were significantly downregulated in all patients. MiR-762 has a significant negative correlation with MST1, LATS2, and YAP protein in lung cancer patients and with MST1 and LATS2 in chronic inflammatory patients. MiR-762 may be involved in the induction of malignant behaviors in lung cancer through suppression of the Hippo pathway. MiR-762, MST1, LATS2, YAP mRNA and protein, TWIST1, and SMAD3 may be effective diagnostic biomarkers in both lung cancer patients and chronic inflammatory patients. High YAP, TWIST1, SMA3 expression, and NSE level are associated with a favorable prognosis for lung cancer.

MACC1 and MET as markers associated with progression and metastasis in cutaneous melanoma.

Cutaneous melanoma is the most common lethal malignancy among skin cancers and has a high propensity for metastasis. Understanding the mechanisms governing tumorigenesis, progression and metastasis as well as identifying biomarkers guiding risk stratification and management of the disease is essential. MACC1 has been found to play key roles in cancer cell migration, invasion, epithelial-to-mesenchymal transition, and metastasis in various types of cancer, through activation of MET signaling. In this study, we examined the extent of MACC1 and MET protein expression by immunohistochemical staining in a tissue microarray constructed from twenty-three melanomas and ten melanocytic nevi. We observed significantly higher levels of MACC1 expression on average in metastatic melanomas, comparing to primary melanomas and nevi. MET expression in metastatic melanomas was also significantly higher than in nevi. MACC1 expression does not appear to correlate with MET expression in nevi and primary melanomas. However, this correlation appears stronger in metastatic melanomas, where seven (78%) of nine cases show intermediate to high expression of both MACC1 and MET. The expressions of MACC1 and MET do not show significant differences based on other clinicopathologic factors including patient age, gender, histologic subtypes, depth of invasion, and staging. Our study suggests that high expression of MACC1 or both MACC1 and MET is associated with metastasis of cutaneous melanoma.

Effect of epidural blockade on immune parameters in the perioperative period: randomized controlled study

BACKGROUND: The potential benefits of anaesthesia techniques in the parameters of cellular immunity and prevention of metastasis in various types of cancer are attracting increasing attention.
 OBJECTIVE: Our aim was to estimate the influence of the epidural blockade as a component of the anesthesia support on the immunity indexes in the patients operated for gastric cancer.
 MATERIALS AND METHODS: 89 patients operated on for gastric cancer, divided into two groups were investigated: in the 1st group (n=27) there was general anesthesia (GA) in combination with extended epidural blockade; in the 2nd group (n=24) GA with postoperative intravenous administration of analgesics. T-cell counts (CD3+, CD4+ CD8+, CD4+/CD8+) and cytokines (IL-4, IL-6, IL-10, INF-y and TNF-a) were determined.
 RESULTS: The CD3+ T-cell levels in both groups were significantly (р 0.05) reduced immediately after surgery. On the 2nd and 3rd day the decrease in CD3+ T-cells was more pronounced (р 0.05) in the 2nd group compared to the 1st group. The content of CD4+ T-cells decreased by the 1st day of the postoperative period (р 0,05) but then gradually increased, the CD4+ level in the 1st group was significantly (р 0.05) higher than in the 2nd group. The changes of CD8+ content between the studied groups were not statistically significant. The immunoregulatory index in both groups decreased by1st day (р 0.05). On the 9th day the index in the 1st group returned to the basic values, while in the 2nd group it remained significantly lower. On the 1st and 3rd day, the levels of IL-4 and IL-6 significantly (р 0.05) increased, while in the 2nd group the levels were higher than in the 1st group (р 0.05). On the 9th day IL-4 and IL-6 indices returned to their initial values. The changes of IL-10 level had a similar pattern, while in the 1st group the rate was significantly higher (р 0.05). At all stages of investigation, the level of IFN- was significantly (р 0.05) higher in the 2nd group, the level of TNF- was higher in the 1st group (р 0.05).
 CONCLUSION: The use of postoperative epidural analgesia during gastric resection for malignant neoplasm is associated with a less suppressive effect on the content of subpopulations of T-lymphocytes and cytokines in comparison with intravenous administration of analgesics and may contribute to the activation of antitumor immune response. Prospective long-term studies are needed to evaluate physician epidural analgesia for oncological outcomes after surgery for gastric cancer.

Metastasis suppressor 1 interacts with protein tyrosine phosphatase receptor-δ to regulate adipogenesis.

Adipogenesis is a finely controlled process and its dysfunction may contribute to metabolic disorders such as obesity. Metastasis suppressor 1 (MTSS1) is a player in tumorigenesis and metastasis of various types of cancers. To date, it is not known whether and how MTSS1 plays a role in adipocyte differentiation. In the current study, we found that MTSS1 was upregulated during adipogenic differentiation of established mesenchymal cell lines and primary cultured bone marrow stromal cells. Gain-of-function and loss-of-function experiments uncovered that MTSS1 facilitated adipocyte differentiation from mesenchymal progenitor cells. Mechanistic explorations revealed that MTSS1 bound and interacted with FYN, a member of Src family of tyrosine kinases (SFKs), and protein tyrosine phosphatase receptor-δ (PTPRD). We demonstrated that PTPRD was capable of inducing the differentiation of adipocytes. Overexpression of PTPRD attenuated the impaired adipogenesis induced by the siRNA targeting MTSS1. Both MTSS1 and PTPRD activated SFKs by suppressing the phosphorylation of SFKs at Tyr530 and inducing the phosphorylation of FYN at Tyr419. Further investigation showed that MTSS1 and PTPRD were able to activate FYN. Collectively, our study has for the first time unraveled that MTSS1 plays a role in adipocyte differentiation in vitro through interacting with PTPRD and thereby activating SFKs such as FYN tyrosine kinase.

A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition.

A disintegrin and metalloprotease 12 (ADAM12) and epithelial‑mesenchymal transition (EMT) are linked in the metastasis of various types of cancer. The present study aimed to assess the ability of ADAM12 to induce EMT and its potential as a therapeutic target for colorectal cancer (CRC). ADAM12 expression in CRC cell lines, CRC tissues and a mouse model of peritoneal metastasis was assessed. The effect of ADAM12 on CRC EMT and metastasis was investigated using ADAM12‑pcDNA6‑myc and ADAM12‑pGFP‑C‑shLenti constructs. ADAM12 overexpression enhanced the proliferation, migration, invasion and EMT of CRC cells. The phosphorylation levels of factors associated with the PI3K/Akt pathway were also increased by ADAM12 overexpression. The knockdown of ADAM12 reversed these effects. ADAM12 expression and the loss of E‑cadherin expression were significantly associated with poorer survival compared with other expression statuses of both proteins. In a mouse model of peritoneal metastasis, overexpression of ADAM12 induced increased tumor weight and peritoneal carcinomatosis index compared with that in the negative control group. Conversely, knockdown of ADAM12 reversed these effects. Furthermore, E‑cadherin expression was significantly decreased by overexpression of ADAM12 compared with in the negative control group. By contrast, E‑cadherin expression was increased by knockdown of ADAM12 compared with in the negative control group. ADAM12 overexpression contributed to CRC metastasis by regulating EMT. In addition, in the mouse model of peritoneal metastasis, ADAM12 knockdown exhibited strong anti‑metastatic action. Consequently, ADAM12 may be considered a therapeutic target for CRC metastasis.

ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5

Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.

Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications.

Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.

Physiological and pathological roles ofHic‑5 in several organs (Review).

Integrins allow cells to adhere to the extracellular matrix and promote the recruitment of other integrins, resulting in the formation of focal adhesion sites at the binding sites. Focal adhesion sites play essential roles in the assembly of the cytoskeleton and are vital in shaping the structure of cells. They also play other regulatory roles by influencing numerous biological functions, such as cell proliferation and apoptosis. Hydrogen peroxide-inducible clone 5 (Hic-5) is a member of the Paxillin family of proteins and is an adhesive plaque scaffolding protein. Its expression can be detected in both vascular and smooth muscle cells. Thus, it plays an essential role in vascular remodeling, as well as in fibrotic diseases. Hic-5 functions as a coactivator of steroid receptors, thus playing a role in steroid hormone-dependent diseases. It also plays a vital role in the invasive metastasis of various types of cancer. Moreover, several studies have demonstrated that Hic-5 plays a critical role in transcriptional regulation, as well as in numerous signaling pathways. Therefore, the inhibition of the functions of Hic-5 may prevent the development or halt the progression of several diseases. Its use as a therapeutic target in future investigations may thus aid in the treatment of several diseases, including various types of cancer. The present review article focused on the expression and functions of Hic-5 in different organs, with the aim of highlighting novel possibilities for future research.

Identification and characterization of slow‑cycling cells in Ewing sarcoma.

Ewing sarcoma (ES) is an aggressive primary malignant bone tumor that predominantly affects children and young adults. Multimodal treatment approaches have markedly improved the survival of patients with localized ES. However, local recurrence and distant metastasis following curative therapies remain a main concern for patients with ES. Recent studies have suggested that slow-cycling cells (SCCs) are associated with tumor progression, local recurrence and distant metastasis in various types of cancers. According to the results of these studies, it was hypothesized that SCCs may play a critical role in tumor progression, chemoresistance and local/distal recurrence in patients with ES. The present study applied a label-retaining system using carboxyfluorescein diacetate succinimidyl ester (CFSE) to identify and isolate SCCs in ES cell lines. In addition, the properties of SCCs, including sphere formation ability, cell cycle distribution and chemoresistance, in comparison with non-SCCs were investigated. RNA sequencing also revealed several upregulated genes in SCCs as compared with non-SCCs; the identified genes not only inhibited cell cycle progression, but also promoted the malignant properties of SCCs. On the whole, the present study successfully identified SCCs in ES cells through a label-retaining system using CFSE. Moreover, to the best of our knowledge, the present study is the first to describe the characteristic properties of SCCs in ES. The findings of this study, if confirmed, may prove to be useful in elucidating the underlying molecular mechanisms and identifying effective therapeutic targets for ES.

Knockdown Wiskott-Aldrich syndrome protein family member 3 (WASF3) inhibits colorectal cancer metastasis and sensitizes to cisplatin through targeting ZNF471

Colorectal cancer (CRC) is a heterogeneous cancer, and many risk factors for colorectal cancer have been established. For CRC metastasis, tumor cell migration, adhesion as well as invasion are important processes. WiskottAldrich syndrome protein family member 3 (WASF3) is necessary for metastasis of various types of cancers. However, its role in CRC progression has not been fully elucidated. This study examined the in vitro functional roles of WASF3 in the CRC and explored the underlying molecular mechanisms. We used siRNA-WASF3 to gene silence WASF3 in colon cancer cell (HCT116) in vitro. The effects of WASF3 silencing on HCT116 cell apoptosis, proliferation, migration, as well as invasion were assessed by flow cytometry, CCK-8, and transwell assays. ZNF471 protein expressions were detected by immunofluorescence staining and RT-PCR. Moreover, the effects of ZNF471 were studied on a series of in vitro antitumor-promoting assays using HCT116. WASF3 knockdown expression using small interfering RNA (siRNA) ameliorated CRC cell proliferation, anchorage-independent growth, invasion, and metastasis. Furthermore, we observed that WASF3 contributed to upregulating the metastasis signaling pathway through inhibiting the expression of ZNF471. Our study suggests that targeting WASF3 signaling might be a novel therapeutic strategy for treating CRC.

Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer.

A limited number of overexpressed transcription factors are associated with cancer progression in many types of cancer. BTB and CNC homology 1 (BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar). It forms heterodimers with the small musculoaponeurotic fibrosarcoma (MAF) proteins and stimulates or suppresses the expression of target genes under a very low intracellular heme concentration. It possesses a significant regulatory role in heme homeostasis, oxidative stress, cell cycle, apoptosis, angiogenesis, and cancer metastasis progression. This review discusses the current knowledge about how BACH1 regulates cancer metastasis in various types of cancer and other carcinogenic associated factors such as oxidative stress, cell cycle regulation, apoptosis, and angiogenesis. Overall, from the reported studies and outcomes, it could be realized that BACH1 is a potential pharmacological target for discovering new therapeutic anticancer drugs.

Circular RNA ubiquitin-associated protein 2 enhances autophagy and promotes colorectal cancer progression and metastasis via miR-582-5p/FOXO1 signaling

Numerous circular RNAs (circRNAs) have been identified as vital regulators in various cancers. The newly reported circular RNA ubiquitin-associated protein 2 (circUBAP2) is a critical player in cell growth and metastasis in various types of cancers, although its role in colorectal cancer (CRC) has yet to be fully elucidated. We find that circUBAP2 is upregulated in CRC tissues and cell lines to induce autophagy both in vitro and in vivo. The effects of circUBAP2 on migration, invasion, and proliferation may be partially related to autophagy. Mechanistically, we uncover that circUBAP2 can directly interact with miR-582-5p and subsequently act as a microRNA sponge to regulate the expression of the miR-582-5p target gene forkhead box protein O1 (FOXO1) and downstream signaling molecules, which collectively advance the progression and metastasis of CRC. These results suggest that circUBAP2 acts as an oncogene via a novel circUBAP2/miR-582-5p/FOXO1 axis, providing a potential biomarker and therapeutic target for CRC management.

Proposed Models of Functional Heterogeneity in Cancer and the Effects of Microenvironmental Factors on Cancer Stem Cells: A Literature Review

Introduction: Functional heterogeneity in cancer may result in the metastasis of various types of tumour cells throughout the body. Attempting to explain functional heterogeneity in cancer cells has given rise to two models. The Cancer Stem Cell model proposes that a subset of tumour cells self-replicate and that heterogeneity is a progeny of various cancer stem cells (CSCs). The Clonal Evolution Model proposes heterogeneity as a product of mutations across tumour cells that accumulate and metastasize linearly or branching. Methods: Research was conducted through open-access journals and information was compiled surrounding CSC models using the Google Scholar and McMaster Library database search engines. Inclusions were sources that detailed the relationship between both models of functional heterogeneity and microenvironments and treatments. Literature that did not center around tumour microenvironments was not included in this literature review. Results: The two main models of tumour proliferation were explored and related to hypoxic tumour microenvironments. Various markers, etiologic agents and toxins were identified that contribute to tumour progression. Cell signalling and pathways that contribute to major cellular functions were identified, along with possible disruptions and epigenetic changes that lead to tumour and CSC proliferation. Discussion: This study reveals that the tumour microenvironment plays a large role in the proliferation of CSCs. Although the therapies targeting microenvironments are in early stages of development, focusing on these CSC targeted- therapies may lead to better treatments for cancer or more effective combination therapies. Strengths of the paper include the compilation of major contributing areas to CSC proliferation, whereas limitations encompass the high variability of tumour cells that are not all covered in this review. Conclusion: While no definitively eradicating treatment for CSCs currently exist, the recent developments in cancer research indicate promising new techniques for its management. Implications: By further studying malignant CSCs, highly effective cancer treatments may result, leading to the advancement of CSC recognition and combination therapy.

Fucosyltransferase 8 regulation and breast cancer suppression by transcription factor activator protein 2γ.

Alterations of glycosyltransferase expression are often associated with tumor occurrence and progression. Among the many glycosyltransferases, increased expression of fucosyltransferase 8 (FUT8) has been frequently observed to be involved in progression and metastasis of various types of cancer. The regulatory mechanisms of FUT8 expression remain unclear. FUT8 expression was shown, in this study, to be elevated in breast cancer. Systematic analysis revealed that transcription factor activator protein 2γ (AP‐2γ) is the target gene of microRNA‐10b (miR‐10b), which we previously identified as a positive regulator of FUT8. Overexpression of AP‐2γ inhibited FUT8 expression, with associated reduction of cell invasiveness and migration ability. AP‐2γ was capable of binding to transcription factor STAT3, and phosphorylation of STAT3 induced transcription of the FUT8 gene. On the basis of our findings, we propose that binding of AP‐2γ to STAT3 results in formation of the AP‐2γ/STAT3 complex and consequent inhibition of STAT3 phosphorylation, thereby preventing entry of p‐STAT3 into the nucleus to initiate FUT8 transcription. This study clarifies the molecular mechanisms whereby transcription factor AP‐2γ regulates FUT8 expression in breast cancer.

STK10 knockout inhibits cell migration and promotes cell proliferation via modulating the activity of ERM and p38 MAPK in prostate cancer cells.

Prostate cancer (PCa) is one of the most common types of cancer and is a serious threat to men's health due to the high rate of incidence and metastasis. However, the exact underlying pathology of this malignant disease has yet to be fully elucidated. The ezrin-radixin-moesin (ERM) family of proteins are associated with the development and metastasis of various types of cancer. Serine threonine kinase 10 (STK10) is an ERM kinase that is involved in the activation of ERM proteins and serves essential roles in the aggregation and adhesion of lymphocytes. To evaluate the functional roles of STK10 in the pathogenesis of PCa, a STK10-knockout (KO) DU145 PCa cell line was generated using the CRISPR-Cas9 gene editing system, and the effects of STK10 deletion on tumor biological behaviors were further analyzed. The present data suggested that STK10 KO promoted PCa cell proliferation by inhibiting p38 MAPK activation and suppressed migration primarily via the inhibition of p38 MAPK signaling and ERM protein activation. To the best of our knowledge, this is the first study to provide evidence that STK10 plays important roles in the proliferation and migration of PCa cells, which will be useful for further investigation into the pathogenesis of this disease.

Prognostic value of SH3PXD2B (Tks4) in human hepatocellular carcinoma: a combined multi-omics and experimental study

BackgroundHepatocellular carcinoma (HCC) is one of the most common and fatal cancers worldwide. HCC invasion and metastasis are crucial for its poor prognosis. SH3PXD2B is a scaffold protein and critical for intravascular and extravascular invasion and metastasis of various types of tumors. However, the role of SH3PXD2B in HCC progression remains unclear.MethodsThe levels of SH3PXD2B mRNA transcripts in the TCGA database and SH3PXD2B protein expression in the Human Protein Atlas were analyzed. Furthermore, the levels of SH3PXD2B expression in clinical samples were analyzed by quantitative RT-PCR and immunohistochemistry. The potential association of the levels of SH3PXD2B expression with clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) of HCC patients was analyzed. The impact of SH3PXD2B silencing by shRNA-based lentivirus transduction on the proliferation and invasion of human HCC Hep3B and Huh7 cells was determined.ResultsSH3PXD2B expression was up-regulated in HCC tissues in the TCGA and Human Protein Atlas as well as clinical samples, relative to that of non-tumor liver samples. The levels of SH3PXD2B expression in HCC tissues were significantly associated with higher HBV infection rate, higher HCC grades and TNM stages, higher Ki-67 expression, higher serum α-fetoprotein (AFP), a shorter OS and RFS of HCC patients. Functionally, SH3PXD2B silencing significantly inhibited the formation and function of invadopodia and the invasion of Hep3B and Huh7 cells, but did not affect their proliferation in vitro.ConclusionsOur data suggest that SH3PXD2B may promote the invasion and metastasis of HCC and be a valuable therapeutic target and biomarker for treatment and prognosis of HCC.

Role of a metastatic suppressor gene KAI1/CD82 in the diagnosis and prognosis of breast cancer.

Globally, breast cancer is the most common type of cancer in females and is one of the leading causes of cancer death in women. The advancement in the targeted therapies and the slight understanding of the molecular cascades of the disease have led to small improvement in the rate of survival of breast cancer patients. However, metastasis and resistance to the current drugs still remain as challenges in the management of breast cancer patients. Metastasis, potentially, leads to failure of the available treatment, and thereby, makes the research on metastatic suppressors a high priority. Tumor metastasis suppressors are several genes and their protein products that have the capability of arresting the metastatic process without affecting the tumor formation. The metastasis suppressors KAI1 (also known as CD82) has been found to inhibit tumor metastasis in various types of solid cancers, including breast cancer. KAI1 was identified as a metastasis suppressor that inhibits the process of metastasis by regulating several mechanisms, including cell motility and invasion, induction of cell senescence, cell–cell adhesion and apoptosis. KAI1 is a member of tetraspanin membrane protein family. It interacts with other tetraspanins, chemokines and integrins to control diverse signaling pathways, which are crucial for protein trafficking and intracellular communication. It follows that better understanding of the molecular events of such genes is needed to develop prognostic biomarkers, and to identify specific therapies for breast cancer patients. This review aims to discuss the role of KAI1/CD82 as a prognosticator in breast cancer.

Analysis of the Prognosis and Therapeutic Value of the CXC Chemokine Family in Head and Neck Squamous Cell Carcinoma.

The CXC chemokines belong to a family which includes 17 different CXC members. Accumulating evidence suggests that CXC chemokines regulate tumor cell proliferation, invasion, and metastasis in various types of cancers by influencing the tumor microenvironment. The different expression profiles and specific function of each CXC chemokine in head and neck squamous cell carcinoma (HNSCC) are not yet clarified. In our work, we analyzed the altered expression, interaction network, and clinical data of CXC chemokines in patients with HNSCC by using the following: the Oncomine dataset, cBioPortal, Metascape, String analysis, GEPIA, and the Kaplan–Meier plotter. The transcriptional level analysis suggested that the mRNA levels of CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL13 increased in HNSCC tissue samples when compared to the control tissue samples. The expression levels of CXCL9, CXCL10, CXCL11, CXCL12, and CXCL14 were associated with various tumor stages in HNSCC. Clinical data analysis showed that high transcription levels of CXCL2, CXCL3, and CXCL12, were linked with low relapse-free survival (RFS) in HNSCC patients. On the other hand, high CXCL14 levels predicted high RFS outcomes in HNSCC patients. Meanwhile, increased gene transcription levels of CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 were associated with a higher overall survival (OS) advantage in HNSCC patients, while high levels of CXCL1, and CXCL8 were associated with poor OS in all HNSCC patients. This study implied that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL12 could be used as prognosis markers to identify low survival rate subgroups of patients with HNSCC as well as be potential suitable therapeutic targets for HNSCC patients. Additionally, CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 could be used as functional prognosis biomarkers to identify better survival rate subgroups of patients with HNSCC.

Epithelial-mesenchymal transition-related circular RNAs in lung carcinoma.

The epithelial-mesenchymal transition (EMT) is a highly complex phenotypic conversion during embryogenesis, and is important for metastasis, which contributes to tumor deterioration and poor prognoses of cancer patients. Lung carcinoma has a high tendency to develop the EMT. Circular RNAs (circRNAs) are involved in EMT-related cell invasion and metastasis in various types of cancers. Moreover, circRNAs have been found to be a link to EMT-related transcription factors and EMT-associated signaling pathways. This review mainly focuses on the influence of EMT-related circRNAs on lung carcinomas. More specifically, the roles of EMT-inducing- and EMT-suppressive circRNAs in lung carcinomas are discussed. With circRNAs potentially becoming promising biomarkers and therapeutic targets for cancer managements, they will hopefully stimulate the interest of medical workers in the early diagnosis, personalized treatment, and positive prognoses in the era of precision oncology.