ARTS Confers Chemoresistance of Breast Cancer by Inducing Apoptosis-Dependent Autophagy via Livin–MDM2–p53 Pathway
Hao Wang, Qianying Guo, Yuting Shen, Keshuo Ding, Yinfeng Chen, Xiaonan Wang, Xing Huang, Zhengsheng Wu
TL;DR
This study shows how a protein called ARTS helps breast cancer cells survive chemotherapy by linking apoptosis and autophagy.
Contribution
The study reveals a novel ARTS–Livin–MDM2–p53 pathway that connects apoptosis and autophagy to promote chemoresistance in breast cancer.
Findings
ARTS is highly expressed in chemoresistant breast cancer tissues and correlates with poor prognosis.
ARTS induces protective autophagy in response to chemotherapy, promoting cancer cell survival.
Blocking autophagy or caspases reduces ARTS-mediated chemoresistance.
Abstract
Apoptosis and autophagy are fundamental pathophysiological programs governing cell fate decisions under stress, particularly during anticancer therapy. However, the interplay between apoptosis and autophagy in cancer chemoresistance remains incompletely understood. Here, we identify the apoptosis-related protein in the transforming growth factor-β signaling pathway (ARTS) as a key molecular transferring apoptotic signal to autophagic machinery to promote cell survival and chemoresistance. ARTS was highly expressed in chemoresistant breast cancer tissues and was associated with poor patient prognosis. ARTS conferred resistance to doxorubicin and docetaxel by inducing protective autophagy in vitro and in vivo cancer models. Mechanistically, upon proapoptotic signaling triggered by chemotherapeutic agents, ARTS translocated from the mitochondrial intermembrane space into the cytosol, where…
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Taxonomy
TopicsAutophagy in Disease and Therapy · Cell death mechanisms and regulation · Cancer-related Molecular Pathways