Cargando…
Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer
Continuous chemotherapy pressure-elicited annexin-A6 (ANXA6)-containing exosome (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...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523856/ https://www.ncbi.nlm.nih.gov/pubmed/34676207 http://dx.doi.org/10.3389/fcell.2021.718721 |
_version_ | 1784585383242104832 |
---|---|
author | Guo, Zihe Guo, Ayao Zhou, Chuang |
author_facet | Guo, Zihe Guo, Ayao Zhou, Chuang |
author_sort | Guo, Zihe |
collection | PubMed |
description | Continuous chemotherapy pressure-elicited annexin-A6 (ANXA6)-containing exosome (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 Yes-associated protein 1 (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 tended to be enriched in the descendent PR-BC cells in contrast with the PS-BC cells. In addition, PR-BC cell-derived exosomes were featured with highly 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 the autophagy inhibitor 3-methyladenine. Moreover, the underlying mechanisms were uncovered, and we evidenced that ANXA6-exo up-regulated 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 BCSC-derived ANXA6-exo facilitated BC progression and PTX resistance, which might help to develop novel treatment strategies for BC in clinic. |
format | Online Article Text |
id | pubmed-8523856 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85238562021-10-20 Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer Guo, Zihe Guo, Ayao Zhou, Chuang Front Cell Dev Biol Cell and Developmental Biology Continuous chemotherapy pressure-elicited annexin-A6 (ANXA6)-containing exosome (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 Yes-associated protein 1 (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 tended to be enriched in the descendent PR-BC cells in contrast with the PS-BC cells. In addition, PR-BC cell-derived exosomes were featured with highly 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 the autophagy inhibitor 3-methyladenine. Moreover, the underlying mechanisms were uncovered, and we evidenced that ANXA6-exo up-regulated 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 BCSC-derived ANXA6-exo facilitated BC progression and PTX resistance, which might help to develop novel treatment strategies for BC in clinic. Frontiers Media S.A. 2021-10-05 /pmc/articles/PMC8523856/ /pubmed/34676207 http://dx.doi.org/10.3389/fcell.2021.718721 Text en Copyright © 2021 Guo, Guo and Zhou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Guo, Zihe Guo, Ayao Zhou, Chuang Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer |
title | Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer |
title_full | Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer |
title_fullStr | Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer |
title_full_unstemmed | Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer |
title_short | Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer |
title_sort | breast cancer stem cell-derived anxa6-containing exosomes sustain paclitaxel resistance and cancer aggressiveness in breast cancer |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523856/ https://www.ncbi.nlm.nih.gov/pubmed/34676207 http://dx.doi.org/10.3389/fcell.2021.718721 |
work_keys_str_mv | AT guozihe breastcancerstemcellderivedanxa6containingexosomessustainpaclitaxelresistanceandcanceraggressivenessinbreastcancer AT guoayao breastcancerstemcellderivedanxa6containingexosomessustainpaclitaxelresistanceandcanceraggressivenessinbreastcancer AT zhouchuang breastcancerstemcellderivedanxa6containingexosomessustainpaclitaxelresistanceandcanceraggressivenessinbreastcancer |