Liang Jui-Lin, Tsai Ming-Hsien, Hsieh Yi-Chun, Liu Huei-Syuan, Chen Shao-Wei, Huang Yung-Yun, Lin Li-Ching, Tsai Tsung-Fu, Liang Yun-Fang, Hsu Wen-Li
Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan 701401, Taiwan, R.O.C.
Department of Surgery, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C.
Oncol Lett. 2023 Jan 24;25(3):92. doi: 10.3892/ol.2023.13678. eCollection 2023 Mar.
Transient receptor potential canonical 7 (TRPC7) has been reported to mediate aging-associated tumorigenesis, but the role of TRPC7 in cancer malignancy is still unclear. TRPC7 is associated with tumor size in patients with lung adenocarcinoma and the present study further evaluated the underlying mechanism of TRPC7 in the regulation of cancer progression. The clinicopathological role of TRPC7 was assessed using immunohistochemistry staining and the pathological mechanism of TRPC7 in lung adenocarcinoma cells was determined using cell cycle examination, invasion and calcium response assays, and immunoblot analysis. The results indicated that high TRPC7 expression was associated with a lower 5-year survival rate compared with low TRPC7 expression, which suggested that TRPC7 expression was inversely associated with overall survival in patients with lung adenocarcinoma. TRPC7 serves a pathological role by facilitating the enhancement of cell growth and migration with increased phosphorylation of Ca/calmodulin-dependent protein kinase II, AKT and ERK. TRPC7 knockdown in lung adenocarcinoma cells restrained cell cycle progression and cell migration by interrupting the TRPC7-mediated Ca signaling-dependent AKT and MAPK signaling pathways. These findings demonstrated for the first time a role of oncogenic TRPC7 in the regulation of cancer malignancy and could provide a novel therapeutic molecular target for patients with lung adenocarcinoma.
据报道，瞬时受体电位香草酸亚型7（TRPC7）介导衰老相关的肿瘤发生，但TRPC7在癌症恶性进展中的作用仍不清楚。TRPC7与肺腺癌患者的肿瘤大小相关，本研究进一步评估了TRPC7在调节癌症进展中的潜在机制。使用免疫组织化学染色评估TRPC7的临床病理作用，并使用细胞周期检查、侵袭和钙反应测定以及免疫印迹分析确定TRPC7在肺腺癌细胞中的病理机制。结果表明，与低TRPC7表达相比，高TRPC7表达与较低的5年生存率相关，这表明TRPC7表达与肺腺癌患者的总生存率呈负相关。TRPC7通过促进细胞生长和迁移增强，伴随钙/钙调蛋白依赖性蛋白激酶II、AKT和ERK磷酸化增加，发挥病理作用。肺腺癌细胞中TRPC7基因敲低通过中断TRPC7介导的钙信号依赖的AKT和MAPK信号通路，抑制细胞周期进程和细胞迁移。这些发现首次证明了致癌性TRPC7在调节癌症恶性进展中的作用，并可为肺腺癌患者提供新的治疗分子靶点。
