Department of Oncology, Shunde Hospital of Southern Medical University (The First People's Hospital of Shunde, Foshan, China.
Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Life Sci. 2019 Oct 15;235:116798. doi: 10.1016/j.lfs.2019.116798. Epub 2019 Aug 28.
Lung cancer is the leading cause for cancer death due to refractory nature to current treatment strategies, understanding the regulatory mechanism of therapy resistance of lung cancer is important for lung cancer therapy. Here, we aimed to study the role of SHCBP1 in lung cancer cisplatin resistance, we found SHCBP1 was upregulated in lung cancer tissues and cells, patients with high SHCBP1 had poor prognosis. SHC binding and spindle associated 1 (SHCBP1) overexpression promoted cisplatin induced apoptosis resistance, migration and invasion determined by apoptosis assay and transwell assay with or without Matrigel, while SHCBP1 knockdown inhibited cisplatin induced apoptosis resistance, migration and invasion. Wnt pathway promoted lung cancer progression, we found SHCBP1 activated Wnt pathway, characterized by promoting β-catenin nuclear translocation. Inhibition of Wnt pathway in SHCBP1 overexpression cells reversed the effect of SHCBP1 overexpression, confirming SHCBP1 promoted lung cancer progression through activating Wnt pathway. We also found SHCBP1 expression was positively corrected with Wnt pathway activity in lung cancer samples. In summary, we found SHCBP1 promoted cisplatin induced apoptosis resistance, migration and invasion through activating Wnt pathway, providing a potential target for lung cancer therapy.
肺癌是癌症死亡的主要原因，由于目前的治疗策略具有难治性，因此了解肺癌治疗耐药的调节机制对于肺癌治疗很重要。在这里，我们旨在研究 SHCBP1 在肺癌顺铂耐药中的作用，我们发现 SHCBP1 在肺癌组织和细胞中上调，SHCBP1 高表达的患者预后不良。SHC 结合和纺锤体相关 1（SHCBP1）过表达促进顺铂诱导的凋亡抵抗，通过有无 Matrigel 的凋亡测定和 Transwell 测定确定迁移和侵袭，而 SHCBP1 敲低抑制顺铂诱导的凋亡抵抗、迁移和侵袭。Wnt 通路促进肺癌进展，我们发现 SHCBP1 激活了 Wnt 通路，表现为促进β-连环蛋白核易位。在 SHCBP1 过表达细胞中抑制 Wnt 通路逆转了 SHCBP1 过表达的作用，证实 SHCBP1 通过激活 Wnt 通路促进肺癌进展。我们还发现 SHCBP1 表达与肺癌样本中的 Wnt 通路活性呈正相关。总之，我们发现 SHCBP1 通过激活 Wnt 通路促进顺铂诱导的凋亡抵抗、迁移和侵袭，为肺癌治疗提供了一个潜在的靶点。
