Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Cancer Sci. 2020 May;111(5):1652-1662. doi: 10.1111/cas.14373. Epub 2020 Mar 25.
Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer-related deaths. Thus, understanding the mechanism of lung cancer metastasis will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF-elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
肺癌是全球最常见的癌症，肺癌转移是癌症相关死亡的主要原因。因此，了解肺癌转移的机制将改善肺癌患者的诊断和治疗。在此，我们发现分化群 109（CD109）的表达与肺腺癌细胞的侵袭和转移能力相关。CD109 在肿瘤组织中上调，CD109 过表达与肺腺癌患者的肿瘤进展、远处转移和预后不良相关。在机制上，CD109 的表达通过与表皮生长因子受体（EGFR）结合来调节蛋白激酶 B（AKT）/雷帕霉素靶蛋白（mTOR）信号通路。抑制 CD109 会降低 EGFR 磷酸化，减少 EGF 诱导的 AKT/mTOR 激活，并使肿瘤细胞对 EGFR 抑制剂敏感。总之，我们的结果表明 CD109 是肺癌患者潜在的诊断和治疗靶点。
