AUTHOR=Guo Zihe , Guo Ayao , Zhou Chuang 

TITLE=Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.718721

DOI=10.3389/fcell.2021.718721

ISSN=2296-634X

ABSTRACT=Continuous chemotherapy pressure-elicited annexin-A6 (ANXA6)-containing exosomes (ANXA6-exo) secretion contributes to paclitaxel (PTX)-resistance in breast cancer (BC), but the molecular mechanisms are not fully elucidated. The present study managed to investigate this issue, and found that ANXA6-exo promoted PTX-resistance and cancer progression in BC cells in a YAP1-dependent manner. Specifically, the parental PTX-sensitive BC (PS-BC) cells were exposed to continuous low-dose PTX to generate PTX-resistant BC (PR-BC) cells, and we found that BC stem cells (BCSCs) tended to be enriched in the descendent PR-BC cells in contrast with the PS-BC cells. In addition, PR-BC cells derived exosomes were featured with high-expressed ANXA6, and ANXA6-exo delivered ANXA6 to promote cell migration, growth, autophagy and stemness in PS-BC cells. Interestingly, ANXA6-exo increased PTX-resistance in PS-BC cells via inducing autophagy, and the effects of ANXA6-exo on PTX-resistance in PS-BC cells were abrogated by co-treating cells with autophagy inhibitor 3-Methyladenine (3-MA). Moreover, the underlying mechanisms were uncovered, and we evidenced that ANXA6-exo upregulated YAP1 to promote Hippo pathway dysregulation, and the promoting effects of ANXA6-exo on PTX-resistance and cancer aggressiveness in BC cells were abrogated by silencing YAP1. Taken together, this study firstly elucidated the underlying mechanisms by which BCSCs-derived ANXA6-exo facilitated BC progression and PTX-resistance, which might help to develop novel treatment strategies for BC in clinic.