Decreased NMIIA heavy chain phosphorylation at S1943 promotes mitoxantrone resistance by upregulating BCRP and N-cadherin expression in breast cancer cells.

Autor:	Li K; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Li T; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Niu Y; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Gao Y; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Shi Y; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., He Y; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Zhang X; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Wang Y; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Cao J; Department of Critical Care Medicine, the First Hospital of Shanxi Medical University, Taiyuan 030001, People's Republic of China., Hu X; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Chen M; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China., Shi R; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, People's Republic of China.
Jazyk:	angličtina
Zdroj:	Biochemistry and cell biology = Biochimie et biologie cellulaire [Biochem Cell Biol] 2024 Jun 01; Vol. 102 (3), pp. 213-225. Date of Electronic Publication: 2024 Jan 08.
DOI:	10.1139/bcb-2023-0232
Abstrakt:	Mitoxantrone (MX) is an effective treatment for breast cancer; however, high efflux of MX that is accomplished by breast cancer resistance protein (BCRP) leads to acquired multidrug resistance (MDR), reducing MX's therapeutic efficacy in breast cancer. Non-muscle myosin IIA (NMIIA) and its heavy phosphorylation at S1943 have been revealed to play key roles in tumor metastasis and progression, including in breast cancer; however, their molecular function in BCRP-mediated MDR in breast cancer remains unknown. In this study, we revealed that the expression of NMIIA heavy chain phosphorylation at S1943 was downregulated in BCRP-overexpressing breast cancer MCF-7/MX cells, and stable expression of NMIIA-S1943A mutant increased BCRP expression and promoted the resistance of MCF-7/MX cells to MX. Meanwhile, NMIIA S1943 phosphorylation induced by epidermal growth factor (EGF) was accompanied by the downregulation of BCRP in MCF-7/MX cells. Furthermore, stable expression of NMIIA-S1943A in MCF-7/MX cells resulted in upregulation of N-cadherin and the accumulation of β-catenin on the cell surface, which inhibited the nucleus translocation of β-catenin and Wnt/β-catenin-based proliferative signaling. EGF stimulation of MCF-7/MX cells showed the downregulation of N-cadherin and β-catenin. Our results suggest that decreased NMIIA heavy phosphorylation at S1943 increases BCRP expression and promotes MX resistance in breast cancer cells via upregulating N-cadherin expression. Competing Interests: The authors declare that there are no conflicts of interest.
Databáze:	MEDLINE
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