Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis

作者全名："Chen, Rui; Li, Peng; Fu, Yan; Wu, Zongyao; Xu, Lijun; Wang, Junhua; Chen, Sha; Yang, Mingzhen; Peng, Bingjie; Yang, Yao; Zhang, Hongwei; Han, Qi; Li, Shuhui"

作者地址："[Chen, Rui; Wu, Zongyao; Xu, Lijun] Tibetan Tradit Med Coll, Lhasa, Peoples R China; [Li, Peng] Yantai Mt Hosp, Yantai, Shandong, Peoples R China; [Fu, Yan; Yang, Yao] Western Theater Command, Gen Hosp, Chengdu, Sichuan, Peoples R China; [Wang, Junhua; Zhang, Hongwei; Han, Qi] Gen Hosp Tibet Area Mil Command, Lhasa, Peoples R China; [Chen, Sha; Yang, Mingzhen; Peng, Bingjie; Han, Qi; Li, Shuhui] Third Mil Med Univ, Army Med Univ, Chongqing, Peoples R China"

通信作者："Han, Q (通讯作者)，Gen Hosp Tibet Area Mil Command, Lhasa, Peoples R China.; Han, Q; Li, SH (通讯作者)，Third Mil Med Univ, Army Med Univ, Chongqing, Peoples R China."

来源：PLOS ONE

ESI学科分类：Multidisciplinary

WOS号：WOS:000949759100004

JCR分区：Q1

影响因子：2.9

年份：2023

卷号：18

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Evidence shows that chaperone-mediated autophagy (CMA) is involved in cancer cell pathogenesis and progression. However, the potential role of CMA in breast cancer angiogenesis remains unknown. We first manipulated CMA activity by knockdown and overexpressing of lysosome-associated membrane protein type 2A (LAMP2A) in MDA-MB-231, MDA-MB-436, T47D and MCF7 cells. We found that the tube formation, migration and proliferation abilities of human umbilical vein endothelial cells (HUVECs) were inhibited after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A knockdown. While the above changes were promoted after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A overexpression. Moreover, we found that CMA could promote VEGFA expression in breast cancer cells and in xenograft model through upregulating lactate production. Finally, we found that lactate regulation in breast cancer cells is hexokinase 2 (HK2) dependent, and knockdown of HK2 can significantly reduce the ability of CMA-mediated tube formation capacity of HUVECs. Collectively, these results indicate that CMA could promote breast cancer angiogenesis via regulation of HK2-dependent aerobic glycolysis, which may serve as an attractive target for breast cancer therapies."

基金机构：National Natural Science Foundation of China [82072946]; Natural Science Foundation of Tibet [XZ202101ZR0109G]

基金资助正文："This work was supported by National Natural Science Foundation of China (82072946) and Natural Science Foundation of Tibet (XZ202101ZR0109G). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."