journal contribution posted on 2023-03-31, 05:02 authored by Hui Wang, Haibo Xu, Wei Chen, Mei Cheng, Li Zou, Qin Yang, Chi Bun Chan, Hao Zhu, Ceshi Chen, Jianyun Nie, Baowei Jiao
Supplementary Data from Rab13 Sustains Breast Cancer Stem Cells by Supporting Tumor–Stroma Cross-talk
National Key Research and Development Program of China
Chinese Academy of Sciences
National Natural Science Foundation of China
“Light of West China” Program
Guolan Ma and Shuangjuan Yang from the Kunming Institute of Zoology
ARTICLE ABSTRACTCancer 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 (BCSC). Rab13 depletion suppressed breast cancer cell stemness, tumorigenesis, and chemoresistance by reducing tumor-stroma cross-talk. Accordingly, Rab13 controlled the membrane translocation of C-X-C chemokine receptor type 1/2 (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 (C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid; 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.
Targeting Rab13 perturbs formation of the breast cancer stem cell niche by inhibiting cross-talk between cancer cells and the tumor microenvironment, providing a therapeutic opportunity for niche-targeted breast cancer treatment.