Lung cancer, the leading cause of cancer-related incidence and mortality worldwide, is characterised by high invasiveness and poor prognosis. Novel therapeutic targets are required, especially for patients with inoperable metastatic disease requiring systemic therapies to improve patients’ welfare. Recently, studies indicated that TMEM176B is a positive regulator in breast and gastric cancers, and it could be a potential target for treatment. In this study, we used single-cell sequencing, proteomics, Co-IP, and in vivo and in vitro experimental models to investigate the role of TMEM176B in lung adenocarcinoma development. Our study indicated that TMEM176B expression was enhanced in lung adenocarcinoma tissues, and it was associated with shorter overall survival (OS). TMEM176B promoted cellular functions, including cell proliferation, invasion, migration and adhesion in vitro and tumour growth in vivo. Moreover, the tube formation ability of endothelial cells was enhanced by treating with the tumour cell-conditioned medium. We have also demonstrated that TMEM176B regulated EMT via the FGFR1/JNK/Vimentin/Snail signalling cascade. Overall, our study suggests TMEM176B could be a potential therapeutic target in lung adenocarcinoma.
肺癌作为全球癌症相关发病率和死亡率的主要原因，其特点是侵袭性强且预后不良。尤其对于需要全身治疗以改善患者生活质量的不可手术转移性疾病患者，亟需寻找新的治疗靶点。近期研究表明，TMEM176B在乳腺癌和胃癌中发挥正向调控作用，可能成为潜在的治疗靶点。本研究通过单细胞测序、蛋白质组学、免疫共沉淀以及体内外实验模型，探讨了TMEM176B在肺腺癌发展中的作用。研究发现，TMEM176B在肺腺癌组织中表达增强，且与较短的总生存期相关。TMEM176B在体外能促进细胞增殖、侵袭、迁移和粘附等细胞功能，在体内则促进肿瘤生长。此外，通过肿瘤细胞条件培养基处理可增强内皮细胞的管腔形成能力。研究还证实TMEM176B通过FGFR1/JNK/Vimentin/Snail信号级联通路调控上皮间质转化。综上所述，本研究提示TMEM176B可能成为肺腺癌的潜在治疗靶点。
肿瘤(癌症)患者之家