CMTM6 Promotes Cell Proliferation and Invasion in Oral Squamous Cell Carcinoma by Interacting with NRP1

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2020 Jul 10

PMID 32642284

Citations 22

Authors

Yang Zheng

Chundi Wang

An Song

Feng Jiang

Junbo Zhou

Gang Li

Jinhai Ye

Xu Ding

Wei Zhang

Yifei Du

Hongchuang Zhang

Heming Wu

Xiaomeng Song

Yunong Wu

Affiliations

Soon will be listed here.

Abstract

Previous studies have identified that both CKLF-like MARVEL transmembrane domain-containing member (CMTM6) and Neuropilin-1 (NRP1) played an essential part in regulating tumorigenesis and immune response. However, the potential connection between CMTM6 and NRP1 in oral squamous cell carcinoma (OSCC) remains unknown. In this study, we investigated the clinicopathologic significance of CMTM6 and NRP1 in OSCC. We examined the co-expression of CMTM6 and NRP1 in both OSCC tissues and cell lines. Co-overexpression of CMTM6 and NRP1 was generally highly expressed in cancer tissues and is associated with poor prognosis. Gain- and loss-of-function assays confirmed the oncogenic properties of CMTM6 in OSCC cells. Depletion of NRP1 abrogated tumorigenesis induced by CMTM6. By performing co-immunoprecipitation (co-IP), we discovered a potential interaction between CMTM6 and NRP1. Meanwhile, the stability of CMTM6 was significantly decreased in the NRP1-silencing cells, indicating the involvement of NRP1 in the degradation process of CMTM6. The crosstalk between CMTM6 and NRP1 provided a new insight into the progression of OSCC, which may indicate an alternative strategy for OSCC treatment.

Citing Articles

Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis.

Li J, Dong X, Kong X, Wang Y, Li Y, Tong Y Biol Direct. 2023; 18(1):48.

PMID: 37592296 PMC: 10436663. DOI: 10.1186/s13062-023-00397-3.

NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation.

Zhang P, Chen L, Zhou F, He Z, Wang G, Luo Y Cell Death Dis. 2023; 14(2):159.

PMID: 36841806 PMC: 9958327. DOI: 10.1038/s41419-023-05696-1.

HNF4G accelerates glioma progression by facilitating NRP1 transcription.

Che H, Zheng Q, Liao Z, Zhang L Oncol Lett. 2023; 25(3):102.

PMID: 36817051 PMC: 9932018. DOI: 10.3892/ol.2023.13688.

CMTM6 as a candidate risk gene for cervical cancer: Comprehensive bioinformatics study.

Huang X, Liu W, Liu C, Hu J, Wang B, Ren A Front Mol Biosci. 2023; 9:983410.

PMID: 36589225 PMC: 9798917. DOI: 10.3389/fmolb.2022.983410.

Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1-Independent Manner.

Long Y, Chen R, Yu X, Tong Y, Peng X, Li F Cancer Immunol Res. 2022; 11(2):241-260.

PMID: 36484740 PMC: 9896022. DOI: 10.1158/2326-6066.CIR-22-0439.

References

Chen C, Zimmermann M, Tinhofer I, Kaufmann A, Albers A . Epithelial-to-mesenchymal transition and cancer stem(-like) cells in head and neck squamous cell carcinoma. Cancer Lett. 2012; 338(1):47-56. DOI: 10.1016/j.canlet.2012.06.013. View

Chen X, Xu D, Li X, Zhang J, Xu W, Hou J . Latest Overview of the Cyclin-Dependent Kinases 4/6 Inhibitors in Breast Cancer: The Past, the Present and the Future. J Cancer. 2019; 10(26):6608-6617. PMC: 6856891. DOI: 10.7150/jca.33079. View

Tripathi S, Levine H, Jolly M . The Physics of Cellular Decision Making During Epithelial-Mesenchymal Transition. Annu Rev Biophys. 2020; 49:1-18. DOI: 10.1146/annurev-biophys-121219-081557. View

Chow L . Head and Neck Cancer. N Engl J Med. 2020; 382(1):60-72. DOI: 10.1056/NEJMra1715715. View

Guan X, Zhang C, Zhao J, Sun G, Song Q, Jia W . CMTM6 overexpression is associated with molecular and clinical characteristics of malignancy and predicts poor prognosis in gliomas. EBioMedicine. 2018; 35:233-243. PMC: 6156716. DOI: 10.1016/j.ebiom.2018.08.012. View

Plein A, Fantin A, Ruhrberg C . Neuropilin regulation of angiogenesis, arteriogenesis, and vascular permeability. Microcirculation. 2014; 21(4):315-23. PMC: 4230468. DOI: 10.1111/micc.12124. View

Chaudhary B, Khaled Y, Ammori B, Elkord E . Neuropilin 1: function and therapeutic potential in cancer. Cancer Immunol Immunother. 2013; 63(2):81-99. PMC: 11028473. DOI: 10.1007/s00262-013-1500-0. View

Vigneswaran N, Williams M . Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 2014; 26(2):123-41. PMC: 4040236. DOI: 10.1016/j.coms.2014.01.001. View

Chu W, Song X, Yang X, Ma L, Zhu J, He M . Neuropilin-1 promotes epithelial-to-mesenchymal transition by stimulating nuclear factor-kappa B and is associated with poor prognosis in human oral squamous cell carcinoma. PLoS One. 2014; 9(7):e101931. PMC: 4084996. DOI: 10.1371/journal.pone.0101931. View

10.

Jin M, Nam A, Park J, Bang J, Bang Y, Oh D . Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer. Cancer Res Treat. 2019; 52(1):149-166. PMC: 6962488. DOI: 10.4143/crt.2019.183. View

11.

Gao F, Chen J, Wang J, Li P, Wu S, Wang J . CMTM6, the newly identified PD-L1 regulator, correlates with PD-L1 expression in lung cancers. Biochem Biophys Rep. 2019; 20:100690. PMC: 6804456. DOI: 10.1016/j.bbrep.2019.100690. View

12.

Vivekanandhan S, Mukhopadhyay D . Genetic status of KRAS influences Transforming Growth Factor-beta (TGF-β) signaling: An insight into Neuropilin-1 (NRP1) mediated tumorigenesis. Semin Cancer Biol. 2018; 54:72-79. PMC: 6072630. DOI: 10.1016/j.semcancer.2018.01.014. View

13.

Li H, Li J, Su Y, Fan Y, Guo X, Li L . A novel 3p22.3 gene CMTM7 represses oncogenic EGFR signaling and inhibits cancer cell growth. Oncogene. 2013; 33(24):3109-18. DOI: 10.1038/onc.2013.282. View

14.

Shiah S, Shieh Y, Chang J . The Role of Wnt Signaling in Squamous Cell Carcinoma. J Dent Res. 2015; 95(2):129-34. DOI: 10.1177/0022034515613507. View

15.

Li C, Shen Z, Bavarian R, Yang F, Bhattacharya A . Oral Cancer: Genetics and the Role of Precision Medicine. Surg Oncol Clin N Am. 2019; 29(1):127-144. DOI: 10.1016/j.soc.2019.08.010. View

16.

Mezzadra R, Sun C, Jae L, Gomez-Eerland R, de Vries E, Wu W . Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature. 2017; 549(7670):106-110. PMC: 6333292. DOI: 10.1038/nature23669. View

17.

Zheng Y, Wang Z, Xiong X, Zhong Y, Dong Y, Li J . Membrane-tethered Notch1 exhibits oncogenic property via activation of EGFR-PI3K-AKT pathway in oral squamous cell carcinoma. J Cell Physiol. 2018; 234(5):5940-5952. DOI: 10.1002/jcp.27022. View

18.

Scanlon C, Van Tubergen E, Inglehart R, DSilva N . Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma. J Dent Res. 2012; 92(2):114-21. PMC: 3545688. DOI: 10.1177/0022034512467352. View

19.

Fazilaty H, Rago L, Youssef K, Ocana O, Garcia-Asencio F, Arcas A . A gene regulatory network to control EMT programs in development and disease. Nat Commun. 2019; 10(1):5115. PMC: 6848104. DOI: 10.1038/s41467-019-13091-8. View

20.

Zheng Y, Wang Z, Ding X, Zhang W, Li G, Liu L . A novel Notch1 missense mutation (C1133Y) in the Abruptex domain exhibits enhanced proliferation and invasion in oral squamous cell carcinoma. Cancer Cell Int. 2018; 18:6. PMC: 5759178. DOI: 10.1186/s12935-017-0496-5. View