Systematic investigation of <scp>CMTM</scp> family genes suggests relevance to glioblastoma pathogenesis and <scp>CMTM</scp>1 and <scp>CMTM</scp>3 as priority targets

Delic, Sabit; Thuy, Andreas; Schulze, Markus; Proescholdt, Martin; Dietrich, Péter; Bosserhoff, Anja‐Katrin; Riemenschneider, Markus J.

doi:10.1002/gcc.22255

Cited by 33 publications

(36 citation statements)

References 25 publications

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“…This family serves major roles in the immune system, male reproductive system and hematopoiesis systems. On the basis of the in‐depth studies in recent years performed by various research groups, a close association between CMTMs and the initiation, development and metastasis of tumors has been demonstrated . A number of studies have shown that CMTM 3, 4, 5, and 8 have been extensively studied as tumor suppressors in multiple types of tumor .…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Huang

Yang

et al. 2019

The Kaohsiung J of Med Scie

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Chemokine‐like factor (CKLF)‐like, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain‐containing family proteins (CMTMs) have significant roles in the immune system, in male reproduction, as well as in tumorigenesis. Previous studies have shown that CMTM family member 7 (CMTM7) was broadly expressed in various normal tissues, but not in lung, gastric, esophageal, pancreas, and cervix cancers. To explore its relationship with liver cancer, we examined the expression of CMTM7 in liver cancers and its correlation with clinical and pathological conditions. We found that CMTM7 expression was markedly reduced in liver cancer tissues, and negatively correlated with TNM staging and tumor metastasis. In vitro studies showed that enforced expression of CMTM7 inhibited the cell growth and migration of liver cancer cells. Further analysis revealed that CMTM7 suppressed AKT signaling and induced cell cycle arrest at the G0/G1 phase in the liver cancer cells, likely as the consequent of decreased levels of cyclin D1, cyclin‐dependent kinase 4 (CDK4), and CDK6, and increased p27 expression. Thus, CMTM7 functions as a tumor suppressor in liver cancer through suppressing cell cycle progression.

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Section: Discussionmentioning

confidence: 99%

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Huang

Yang

et al. 2019

The Kaohsiung J of Med Scie

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“…Mechanistically, CMTM3 regulated the STAT3/Twist1/EMT signaling pathway (13). Although the positive role of CMTM3 in cancer progression has been demonstrated (25), it is well accepted to be a tumor suppressor. Previous studies have suggested that promoter hypermethylation is involved in the decreased expression of CMTM3 in various types of cancer, including gastric, colorectal and breast cancer (11,12,26).…”

Section: Discussionmentioning

confidence: 99%

miR-135b-5p promotes gastric cancer progression by targeting CMTM3

Huang

Sun

et al. 2017

Int J Oncol

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CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) is considered to be a tumor suppressor gene in multiple types of malignancies. Previous studies have indicated that CMTM3 suppresses metastasis and epithelial-mesenchymal transition (EMT) in gastric cancer. However, its role in gastric cancer cell proliferation has rarely been discussed. Moreover, the regulatory mechanisms of CMTM3 in gastric cancer remain unclear. In this study, RT‑qPCR and IHC were used to assess the expression of CMTM3 and miR‑135b‑5p in gastric cancer tissues and cell lines. We found that the expression of miR‑135b‑5p was negatively associated with CMTM3 in gastric cancer tissues, and we verified that miR‑135b‑5p directly targeted CMTM3 in gastric cancer cells by dual-luciferase reporter assay. CCK8 assay, Transwell assay and flow cytometric analysis were conducted to examine the functions of CMTM3 and miR‑135b‑5p in vitro. Our results demonstrated that the overexpression of CMTM3 or the suppression of miR‑135b‑5p using an inhibitor suppressed SGC‑7901 gastric cancer cell proliferation, invasion and cell cycle progression, and promoted SGC‑7901 cell apoptosis. Furthermore, a BALB/c nude mouse subcutaneous xenograft model was used to verify the function of miR‑135b‑5p and CMTM3. Our results revealed that miR‑135b‑5p inhibitor significantly suppressed SGC‑7901 cell tumorigenesis in vivo. In addition, IHC revealed that CMTM3 expression was markedly increased in tumors infected with miR‑135b‑5p inhibitor lentivirus. On the whole, the findings of the present study suggest that the overexpression of miR‑135b‑5p inhibits CMTM3 expression, and promotes gastric cancer progression and metastasis. Our findings provide a novel therapeutic target for gastric cancer.

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“…These findings all proved that CMTM3 had a suppressive function in tumor progression. Only one study presented the oncogenic effects of CMTM3 in glioblastoma by Delic, in which CMTM1, 3, and 7 were proved to promote the abilities of tumor cell invasion, and higher CMTM1 and 3 expressions significantly correlated with shorter overall survivals [26]. To further explore the potential tumor-suppressive mechanisms of CMTM3 in cancers, several studies were performed and concluded as follows: (i) the silence of CMTM3 was due to aberrant promoter CpG methylation that could be reversed by pharmacologic demethylation [16,[27][28][29]; (ii) the expression of MMP2 and the phosphorylation of Erk1/2 were decreased when CMTM3 was restored [13,15]; (iii) CMTM3 induced a cell cycle arrest of G2 phase and apoptosis by upregulating the expression of p21 and increasing the cleavage of caspase 9, 8, 3 and PARP [16]; (iv) CMTM3 inhibited EMT through the STAT3/Twist1/EMT or JAK2/ STAT3 signaling pathway [14,17].…”

Section: Discussionmentioning

confidence: 99%

The prognostic significance of CMTM3 in colorectal cancer and association with the phenomenon of EMT

Chen¹,

Ren²,

Zhao³

et al. 2018

Oncotarget

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CKLF-like MARVEL transmembrane domain containing 3 (CMTM3), which is located at the critical tumor suppressor locus 16q22.1, has been proposed as a putative tumor suppressor gene in multiple types of malignancies. However, its role in colorectal cancer (CRC) has not been clearly defined. In this study, the potential relationships between CMTM3 and epithelial-mesenchymal transition (EMT)-related proteins were firstly analyzed in the clinical tissues. Our data demonstrated that CMTM3 presented a relatively negative staining in 130 CRC tissues, compared to their corresponding normal-appearing tissues (NATs) (P < 0.05). The reduction of CMTM3 protein was associated with the advanced depth of invasion, distant metastasis and tumor stage (P < 0.05). CRC patients with low CMTM3 levels had a poorer 5-year overall survival (OS) rate (P = 0.035), and the decreased level of CMTM3 could be served as an independent and significant prognostic factor of CRC patients (P = 0.013). Meanwhile, a significant positive relationship between CMTM-3 and E-cadherin was found (r = 0.253, P = 0.004), whereas CMTM3 negatively correlated with Vimentin (r = −0.506 P = 0.000). To better understand the tumor suppressing effect of CMTM3 in CRC progression through an EMT-dependent mechanism, we found that up-regulation of CMTM3 significantly suppressed the abilities of cell proliferation, migration and invasion in CRC cells in vitro (P < 0.05). The results of western blot analysis also disclosed that CMTM3 influenced the expressions of EMT-related proteins (E-cadherin, N-cadherin and Vimentin) (P < 0.05). These results suggested that CMTM3 might be involved in the EMT process of CRC, and could be considered as a potentially important molecular treatment strategy for early stage CRC patients.

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Systematic investigation of CMTM family genes suggests relevance to glioblastoma pathogenesis and CMTM1 and CMTM3 as priority targets

Cited by 33 publications

References 25 publications

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

miR-135b-5p promotes gastric cancer progression by targeting CMTM3

The prognostic significance of CMTM3 in colorectal cancer and association with the phenomenon of EMT

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