THBS4 silencing regulates the cancer stem cell-like properties in prostate cancer via blocking the PI3K/Akt pathway
THBS4 silencing regulates the cancer stem cell-like properties in prostate cancer via blocking the PI3K/Akt pathway
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DOI：
10.1002/pros.23989
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发表时间：
2020-05-18
期刊：
影响因子：
2.8
通讯作者：
Huo, Wei
中科院分区：
文献类型：
--
作者：
Hou, Yi;Li, Hai;Huo, Wei
背景尽管血小板反应蛋白4（TMBS 4）参与控制前列腺癌（PCa）的生物学，但这种调节的机制仍不清楚。因此，本研究旨在探讨THBS 4对PCa干细胞样特性的调控作用及其与磷脂酰肌醇3 '-激酶（PI 3 K）/蛋白激酶B（Akt）信号通路相关的可能机制。THBS 4在PCa干细胞中过表达或沉默，随后评估PCa干细胞的自我更新、增殖、细胞周期分布和凋亡以及体内致瘤性。结果THBS 4在PCa干细胞中的表达水平高于PCa细胞。过表达THBS 4可促进PCa干细胞的自我更新和增殖，抑制其凋亡，增强其体内致瘤性，这是通过激活PI 3 K/Akt通路实现的。结论THBS 4基因沉默可通过阻断PI 3 K/Akt信号通路抑制PCa细胞的CSC样特性，为PCa的治疗提供了新的靶点。
Background Although thrombospondins 4 (THBS4) participates in controlling the biology of prostate cancer (PCa), the mechanism underlying this regulation remains unknown. Hence, this study aims to identify the regulatory effects of THBS4 on the PCa stem cell-like properties and the potential mechanism associated with the phosphatidylinositol 3 '-kinase (PI3K)/protein kinase B (Akt) pathway.Methods PCa stem cells were sorted and identified using flow cytometry and THBS4 expression in the identified PCa stem cells was measured using Western blot assay. THBS4 was overexpressed or silenced in PCa stem cells, following which, self-renewal, proliferation, cell cycle distribution, and apoptosis of PCa stem cells were assessed as well as tumorigenicity in vivo was evaluated. PI3K/Akt pathway inhibitor was applied to identify its involvement in the regulatory roles of THBS4 in PCa stem cells.Results THBS4 was expressed at a higher level in PCa stem cells than in PCa cells. The overexpression of THBS4 promoted the self-renewal and proliferation, curbed the apoptosis of PCa stem cells, and enhanced the in vivo tumorigenicity, which was achieved by activating the PI3K/Akt pathway. On the contrary, short-hairpin RNA-mediated silencing of THBS4 exhibited suppressive effects on those cancer stem cell (CSC)-like properties and promotive effects on their apoptosis.Conclusion THBS4 silencing can impede the CSC-like properties in PCa via blockade of the PI3K/Akt pathway, which provides patients with PCa a new therapeutic target.