Abstract：
:Breast cancer stem cells (BCSCs) play a critical role in tumor recurrence and metastasis. Exposure of breast cancer cells to chemotherapy leads to an enrichment of BCSCs. Here, we find that chemotherapy induces the expression of glutathione S-transferase omega 1 (GSTO1), which is dependent on hypoxia-inducible factor 1 (HIF-1) and HIF-2. Knockdown of GSTO1 expression abrogates carboplatin-induced BCSC enrichment, decreases tumor initiation and metastatic capacity, and delays tumor recurrence after chemotherapy. GSTO1 interacts with the ryanodine receptor RYR1 and promotes calcium release from the endoplasmic reticulum. Increased cytosolic calcium levels activate PYK2 → SRC → STAT3 signaling, leading to increased expression of pluripotency factors and BCSC enrichment. HIF inhibition blocks chemotherapy-induced GSTO1 expression and BCSC enrichment. Combining HIF inhibitors with chemotherapy may improve clinical outcome in breast cancer.
journal_name
Cell Repjournal_title
Cell reportsauthors
Lu H,Chen I,Shimoda LA,Park Y,Zhang C,Tran L,Zhang H,Semenza GLdoi
10.1016/j.celrep.2017.02.001subject
Has Abstractpub_date
2017-02-21 00:00:00pages
1946-1957issue
8issn
2211-1247pii
S2211-1247(17)30165-1journal_volume
18pub_type
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