Zheng Yang, Wang Chundi, Song An, Jiang Feng, Zhou Junbo, Li Gang, Zhang Wei, Ye Jinhai, Ding Xu, Zhang Wei, Du Yifei, Zhang Hongchuang, Wu Heming, Song Xiaomeng, Wu Yunong
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University Nanjing, China.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomotology, Nanjing Medical University Nanjing, China.
Am J Cancer Res. 2020 Jun 1;10(6):1691-1709. eCollection 2020.
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.
先前的研究已经确定,含CKLF样MARVEL跨膜结构域成员(CMTM6)和神经纤毛蛋白-1(NRP1)在调节肿瘤发生和免疫反应中都起着至关重要的作用。然而,CMTM6与NRP1在口腔鳞状细胞癌(OSCC)中的潜在联系仍不清楚。在本研究中,我们调查了CMTM6和NRP1在OSCC中的临床病理意义。我们检测了CMTM6和NRP1在OSCC组织和细胞系中的共表达情况。CMTM6和NRP1的共过表达在癌组织中通常高度表达,且与预后不良相关。功能获得和功能丧失实验证实了CMTM6在OSCC细胞中的致癌特性。NRP1的缺失消除了CMTM6诱导的肿瘤发生。通过进行免疫共沉淀(co-IP),我们发现CMTM6和NRP1之间存在潜在的相互作用。同时,在NRP1沉默的细胞中,CMTM6的稳定性显著降低,表明NRP1参与了CMTM6的降解过程。CMTM6和NRP1之间的相互作用为OSCC的进展提供了新的见解,这可能为OSCC治疗指明了一种替代策略。