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EEF1A2 triggers stronger ERK mediated metastatic program in ER negative breast cancer cells than in ER positive cells.

Life Sci. 2020 Dec 01;262:118553. Epub 2020 Oct 07
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摘要


AIMS:Ever since EEF1A2's identification as a putative oncogene in breast cancer, it has stimulated curiosity due to its contrasting role in predicting the prognostic values in breast cancer patients. Contradicting reports suggest it to be playing a pro-survival as well as a negative role in the survival of patients. This prompted us to find the association of this protein with molecular subtypes in breast cancer and its effect on EMT in representative cell lines. MAIN METHODS:Data-mining was carried out to ascertain the correlation of EEF1A2 with molecular subtypes in breast cancer patients. Scratch wound healing and transwell invasion assays were carried out to assess its role in migration and invasion. Western blot, qRT-PCR, and ELISA were carried out to determine key signalling pathways, cytokines, and EMT factors responsible for the observed phenotype. KEY FINDINGS:EEF1A2 was associated with ER receptor positivity in breast cancer and was involved in its transcriptional regulation. It induced a robust metastatic program in MDA-MB-231 (a triple-negative cell line), and induced significant changes in its invasive and migratory properties via activation of the ERK pathway. This was not the case in MCF7 which is an ER-positive cell line. SIGNIFICANCE:We highlight the specific tendency of EEF1A2 to enhance invasive properties of cell lines in particular molecular subtype only. This sheds light on its selective role in regulating oncogenic processes in breast cancer and could explain its contradicting association with good survival, despite being an oncogene in a certain cohort of breast cancer patients.

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