CMTM1_v17 is a novel potential therapeutic target in breast cancer

Wang,Jing; Zhang,Guoying; Zhang,Yingmei; Luo,Yang; Song,Quansheng; Qiu,Xiaoyan; Mo,Xiaoning; Wang,Lu

doi:10.3892/or.2014.3429

CMTM1_v17 is a novel potential therapeutic target in breast cancer

Authors:
- Jing Wang
- Guoying Zhang
- Yingmei Zhang
- Yang Luo
- Quansheng Song
- Xiaoyan Qiu
- Xiaoning Mo
- Lu Wang
View Affiliations

Affiliations: Department of Immunology, Center for Human Disease Genomics, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P.R. China
Published online on: August 20, 2014 https://doi.org/10.3892/or.2014.3429
Pages: 1829-1836

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing 1 (CMTM1) consists of at least 23 alternatively spliced isoforms designated CMTM1_v1-v23. In the present study, we detected CMTM1_v17 expression in multiple human normal and tumor tissues and found that CMTM1_v17 was highly expressed in testis and many tumor tissues including breast tumor. The overexpression of CMTM1_v17 in the breast cancer cell line MDA-MB-231 promoted cell proliferation and resistance to tumor necrosis factor-α (TNF-α)-induced apoptosis. Moreover, siRNA-mediated silencing of CMTM1_v17 sensitized MDA-MB-231 cells to TNF-α-induced apoptosis. We propose that CMTM1_v17 may be a novel potential target for therapy in breast cancer patients. The present study provides insight into a novel mechanism by which CMTM1_v17 enhances cellular proliferation and abrogates TNF-α-induced apoptosis. These findings also have implications for clinical practice as they highlight the potential for therapeutic targeting of CMTM1_v17 for the treatment of breast and other cancers in which CMTM1_v17 impacts cellular proliferation and survival.

View Figures

View References

1	Han W, Lou Y, Tang J, et al: Molecular cloning and characterization of chemokine-like factor 1 (CKLF1), a novel human cytokine with unique structure and potential chemotactic activity. Biochem J. 357:127–135. 2001. View Article : Google Scholar : PubMed/NCBI
2	Han W, Ding P, Xu M, et al: Identification of eight genes encoding chemokine-like factor superfamily members 1–8 (CKLFSF1–8) by in silico cloning and experimental validation. Genomics. 81:609–617. 2003.PubMed/NCBI
3	Xia D, Li X, Lou Y, et al: Overexpression of chemokine-like factor 2 promotes the proliferation and survival of C2C12 skeletal muscle cells. Biochim Biophys Acta. 1591:163–173. 2002. View Article : Google Scholar : PubMed/NCBI
4	Lou Y, Xia D, Han W, et al: Molecular cloning and characterization of rat chemokine-like factor 1 and 2. Gene. 307:125–132. 2003. View Article : Google Scholar : PubMed/NCBI
5	Rui M, Xia D, Zhang Y, et al: Molecular cloning and characterization of four isoforms of mCKLF, mouse homologues of human chemokine-like factor. Mol Biol Rep. 30:229–237. 2003. View Article : Google Scholar : PubMed/NCBI
6	Wang L, Wu C, Zheng Y, et al: Molecular cloning and characterization of chemokine-like factor super family member 1 (CKLFSF1), a novel human gene with at least 23 alternative splicing isoforms in testis tissue. Int J Biochem Cell Biol. 36:1492–1501. 2004. View Article : Google Scholar : PubMed/NCBI
7	Di Meo S, Airoldi I, Sorrentino C, Zorzoli A, Esposito S and Di Carlo E: Interleukin-30 expression in prostate cancer and its draining lymph nodes correlates with advanced grade and stage. Clin Cancer Res. 20:585–594. 2014.PubMed/NCBI
8	Shi S, Rui M, Han W, et al: CKLFSF2 is highly expressed in testis and can be secreted into the seminiferous tubules. Int J Biochem Cell Biol. 37:1633–1640. 2005. View Article : Google Scholar : PubMed/NCBI
9	Jin C, Ding P, Wang Y and Ma D: Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8. FEBS Lett. 579:6375–6382. 2005. View Article : Google Scholar : PubMed/NCBI
10	Zhong J, Wang Y, Qiu X, et al: Characterization and expression profile of CMTM3/CKLFSF3. J Biochem Mol Biol. 39:537–545. 2006. View Article : Google Scholar : PubMed/NCBI
11	Plate M, Li T, Wang Y, et al: Identification and characterization of CMTM4, a novel gene with inhibitory effects on HeLa cell growth through inducing G2/M phase accumulation. Mol Cells. 29:355–361. 2010. View Article : Google Scholar : PubMed/NCBI
12	Shao L, Cui Y, Li H, et al: CMTM5 exhibits tumor suppressor activities and is frequently silenced by methylation in carcinoma cell lines. Clin Cancer Res. 13:5756–5762. 2007. View Article : Google Scholar
13	Wang Y, Li J, Cui Y, et al: CMTM3, located at the critical tumor suppressor locus 16q22.1, is silenced by CpG methylation in carcinomas and inhibits tumor cell growth through inducing apoptosis. Cancer Res. 69:5194–5201. 2009. View Article : Google Scholar
14	Li H, Li J, Su Y, et al: A novel 3p22.3 gene CMTM7 represses oncogenic EGFR signaling and inhibits cancer cell growth. Oncogene. 33:3109–3118. 2014. View Article : Google Scholar : PubMed/NCBI
15	Liu JC, Voisin V, Bader GD, et al: Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2⁺:ERα⁻ breast cancer. Proc Natl Acad Sci USA. 109:5832–5837. 2012. View Article : Google Scholar
16	Locksley RM, Killeen N and Lenardo MJ: The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 104:487–501. 2001. View Article : Google Scholar : PubMed/NCBI
17	Baldwin AS: Regulation of cell death and autophagy by IKK and NF-κB: critical mechanisms in immune function and cancer. Immunol Rev. 246:327–345. 2012.