Autophagy Supports Breast Cancer Stem Cell Maintenance by Regulating IL6 Secretion.
Autophagy Supports Breast Cancer Stem Cell Maintenance by Regulating IL6 Secretion.
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DOI：
10.1158/1541-7786.mcr-14-0487
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发表时间：
2015-04
期刊：
影响因子：
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通讯作者：
Thorburn A
中科院分区：
文献类型：
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作者：
Maycotte P;Jones KL;Goodall ML;Thorburn J;Thorburn A
自噬是细胞在应激期间降解细胞物质以提供生存所需的营养和能量的机制。自噬被认为是癌症干细胞（CSC）或肿瘤起始细胞维持的关键过程，但自噬支持CSC存活的机制仍知之甚少。在这项研究中，通过敲低ATG 7或BECN 1抑制自噬，通过调节CD 24和IL 6分泌来修饰乳腺癌细胞中的CD 44 +/CD 24低/−群体。在独立于自噬存活的乳腺癌细胞系中，自噬抑制增加了IL 6向培养基的分泌。另一方面，在自噬依赖性细胞系中，自噬抑制降低了IL 6分泌、细胞存活和乳腺球形成。在这些细胞中，IL 6处理或自噬感受态细胞的条件培养基挽救了自噬抑制诱导的乳腺球形成缺陷。这些结果表明，自噬通过调节IL 6分泌来调节自噬依赖性乳腺癌细胞中的乳腺CSC维持，这暗示自噬是乳腺癌中的潜在治疗靶点。
Autophagy is a mechanism by which cells degrade cellular material to provide nutrients and energy for survival during stress. The autophagy is thought to be a critical process for cancer stem (CSC) or tumor initiating cell maintenance but the mechanisms by which autophagy supports survival of CSCs remain poorly understood. In this study, inhibition of autophagy by knockdown of ATG7 or BECN1 modified the CD44+/CD24low/− population in breast cancer cells by regulating CD24 and IL6 secretion. In a breast cancer cell line that is independent of autophagy for survival, autophagy inhibition increased IL6 secretion to the media. On the other hand, in an autophagy-dependent cell line, autophagy inhibition decreased IL6 secretion, cell survival and mammosphere formation. In these cells, IL6 treatment or conditioned media from autophagy-competent cells rescued the deficiency in mammosphere formation induced by autophagy inhibition. These results reveal that autophagy regulates breast CSC maintenance in autophagy-dependent breast cancer cells by modulating IL6 secretion implicating autophagy as a potential therapeutic target in breast cancer.