Rab13 Sustains Breast Cancer Stem Cells by Supporting Tumor-stroma Crosstalk

author:	Hui Wang, Haibo Xu, Wei Chen, Mei Cheng, Li Zou, Qin Yang, Chi Bun Chan, Hao Zhu, Ceshi Chen, Jian-Yun Nie, Baowei Jiao
Abstract:	Cancer stem cells (CSC) are supported by the tumor microenvironment, and non-CSCs can regain CSC phenotypes in certain niches, leading to limited clinical benefits of CSC-targeted therapy. A better understanding of the mechanisms governing the orchestration of the CSC niche could help improve the therapeutic targeting of CSCs. Here, we report that Rab13, a small GTPase, is highly expressed in breast CSCs (BCSCs). Rab13 depletion suppressed breast cancer cell stemness, tumorigenesis, and chemoresistance by reducing tumor-stroma crosstalk. Accordingly, Rab13 controlled the membrane translocation of CXCR1/2, allowing tumor cells to interact with tumor-associated macrophages and cancer-associated fibroblasts to establish a supportive BCSC niche. Targeting the Rab13-mediated BCSC niche with bardoxolone-methyl (CDDO-Me) prevented BCSC stemness in vitro and in vivo. These findings highlight the novel regulatory mechanism of Rab13 in BCSC, with important implications for the development of therapeutic strategies for disrupting the BCSC niche
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PubYear:	2022
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Unit code:	152453
Publication name:	Cancer Research
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Paper source:	https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-21-4097/694330/Rab13-sustains-breast-cancer-stem-cells-by?redirectedFrom=fulltext
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