BIRC5：肺癌干细胞和神经胶质瘤干细胞的新治疗靶点。

BIRC5: A novel therapeutic target for lung cancer stem cells and glioma stem cells.

机构信息

Department of Environmental Safety Technology Research, Korea Atomic Energy Research Institute, Yuseong-Gu, Daejeon, 34057, Republic of Korea; Department of Radiation Life Science, Korea University of Science and Technology, Yuseong-Gu, Daejeon, 34113, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2023 Nov 19;682:141-147. doi: 10.1016/j.bbrc.2023.10.008. Epub 2023 Oct 4.

DOI:10.1016/j.bbrc.2023.10.008

PMID:37806253

Abstract

Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) is also known as survivin. BIRC5, a member of the apoptosis inhibitor (IAP) family, negatively regulates apoptosis or programmed cell death by inhibiting caspase activation. Due to these properties, overexpression of BIRC5 enables specific survival and division associated with cancer malignancies. In addition, BIRC5 is highly expressed in stem cells, but not present at all in terminally differentiated cells. On this basis, there is speculation that BIRC5 may be involved in the regulation of cancer stem cells (CSCs), but few study results have been reported. In addition, the molecular mechanisms of BIRC5 regulation are not yet well understood. Through the present study, it was confirmed that BIRC5 is a key factor regulating CSCs and epithelial to mesenchymal transition (EMT). BIRC5 was simultaneously overexpressed in lung cancer stem cells (LCSCs) and glioma stem cells (GSCs), and when the expression was suppressed, the characteristics of CSCs disappeared. In addition, plasminogen activator inhibitor-1 (PAI-1), a secreted factor regulated by BIRC5, is involved in signaling mechanisms that regulate cancer stem cells and EMT, and PAI-1 forms an autocrine chain. Based on these results, BIRC5 is proposed as a novel therapeutic target protein for LCSCs and GSCs.

摘要

杆状病毒 IAP 重复蛋白 5（Baculoviral inhibitor of apoptosis repeat containing 5，BIRC5）也被称为存活素。BIRC5 是凋亡抑制剂（IAP）家族的成员，通过抑制半胱天冬酶的激活来负调控细胞凋亡或程序性细胞死亡。由于这些特性，BIRC5 的过表达使与癌症恶性肿瘤相关的特定存活和分裂成为可能。此外，BIRC5 在干细胞中高度表达，但在终末分化细胞中完全不存在。在此基础上，有人推测 BIRC5 可能参与调节癌症干细胞（CSC），但报道的研究结果很少。此外，BIRC5 的调控分子机制尚不清楚。通过本研究证实，BIRC5 是调节 CSCs 和上皮间质转化（EMT）的关键因素。BIRC5 同时在肺癌干细胞（LCSC）和神经胶质瘤干细胞（GSC）中过表达，当表达受到抑制时，CSC 的特征消失。此外，BIRC5 调节的分泌因子纤溶酶原激活物抑制剂-1（plasminogen activator inhibitor-1，PAI-1）参与调节癌症干细胞和 EMT 的信号机制，并且 PAI-1 形成自分泌链。基于这些结果，BIRC5 被提议作为 LCSC 和 GSC 的新型治疗靶蛋白。