HBXIP induces anoikis resistance by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis and stabilize Prdx1 in breast cancer.

ABSTRACT: Anoikis resistance is an essential prerequisite for tumor metastasis, but the underlying molecular mechanisms remain unknown. Herein, we report that the oncoprotein hepatitis B X-interacting protein (HBXIP) is prominently upregulated in breast cancer cells following ECM detachment. Altering HBXIP expression can impair the anchorage-independent growth ability of tumor cells. Mechanistically, HBXIP, which binds to Kelch-like ECH-associated protein 1 (Keap1) to activate nuclear factor E2-related factor 2 (Nrf2), contains a cis-acting antioxidant response element (ARE) in the gene promoter and is a target gene of Nrf2. The HBXIP/Nrf2 axis forms a reciprocal positive feedback loop that reinforces the expression and tumor-promoting actions of each protein. In response to ECM detachment, Nrf2 red

SUBMITTER: Zhou X 

PROVIDER: S-EPMC8758767 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature