BAF53A drives colorectal cancer development by regulating DUSP5-mediated ERK phosphorylation

Autor: Ziqing Yang, Dandan Huang, Manqi Meng, Wencong Wang, Junyan Feng, Lekun Fang, Honglei Chen, Shaomin Zou
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Death and Disease, Vol 13, Iss 12, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-022-05499-w
Popis: Abstract BAF53A, an important subunit of the SWI/SNF epigenetic chromatin regulatory complex, has been implicated as the driver of diverse cancers. However, the role of BAF53A in colorectal cancer (CRC) remains poorly understood. Here, we examined the expression of BAF53A in CRC samples and observed that BAF53A was significantly upregulated in CRC tissues compared with paired adjacent normal tissues. In vitro and in vivo studies suggested that ectopic expression of BAF53A promoted colorectal cancer cell proliferation, colony formation, and tumorigenesis, whereas knockdown of BAF53A hindered these cellular functions. DUSP5 (dual-specificity phosphatase 5), an ERK1/2-specific endogenous phosphatase, was expressed at low levels in CRC. We found a negative correlation between BAF53A and DUSP5 expression in a set of CRC samples. Mechanistic studies revealed that P63 was a potential transcription repressor of DUSP5. BAF53A could interact with P63, decreasing the DUSP5 expression level and subsequently promoting ERK1/2 phosphorylation. Thus, our study provides insights into the applicability of the BAF53A-DUSP5-ERK1/2 axis as a potential therapeutic target in CRC.
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