Zhang Yan, Zhang Xueyan, Huang Jinsu, Dong Qianggang
Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, 25/Ln 2200 Xietu Road, Shanghai, 200032, People's Republic of China.
Med Oncol. 2015 May;32(5):157. doi: 10.1007/s12032-015-0596-9. Epub 2015 Apr 4.
The refractory pulmonary adenocarcinoma is characterized by its metastasis and resistance to cytotoxic agents. While the underlying molecular mechanism is unclear, the property of chemoresistance may mainly lie in the presence of highly resistant cancer stem cells. We examined the function of Wnt/β-catenin signaling in maintaining cancer stem cells (CSCs) in lung adenocarcinoma. Lentivirus-mediated knockdown of β-catenin expression accelerated cell cycle. Subsequently, β-catenin knockdown PC9 cells improve the sensitivity to chemotherapy. Further focusing on Wnt signal by administrating PP and EGFR-TKIs as Wnt antagonists can decrease metastasis and induce apoptosis. Collectively, these results indicate that Wnt signaling pathway plays an essential role in maintaining highly resistant CSCs, regulation of cell cycle, metastasis and apoptosis in lung adenocarcinoma.
难治性肺腺癌的特征在于其转移和对细胞毒性药物的抗性。虽然潜在的分子机制尚不清楚，但化疗抗性的特性可能主要在于存在高度抗性的癌症干细胞。我们研究了Wnt/β-连环蛋白信号通路在维持肺腺癌癌症干细胞（CSCs）中的作用。慢病毒介导的β-连环蛋白表达敲低加速了细胞周期。随后，β-连环蛋白敲低的PC9细胞提高了对化疗的敏感性。通过施用PP和EGFR-TKIs作为Wnt拮抗剂进一步聚焦Wnt信号，可以减少转移并诱导凋亡。总体而言，这些结果表明Wnt信号通路在维持肺腺癌中高度抗性的CSCs、调节细胞周期、转移和凋亡方面起着至关重要的作用。
