Aspirin inhibits epithelial-to-mesenchymal transition and migration of oncogenic K-ras-expressing non-small cell lung carcinoma cells by down-regulating E-cadherin repressor Slug

BMC Cancer
Poulami KhanTanya Das

Abstract

Cancer metastasis is one of the most common causes of treatment failure and death in cancer patients. It has been acknowledged that aberrant activation of epithelial-to-mesenchymal transition (EMT) program, endows cancer cells with metastatic competence for which E-cadherin switch is a well-established hallmark. Suppression of E-cadherin by its transcriptional repressor Slug is thus a determining factor for EMT. Here, we aimed at discerning (i) the molecular mechanisms that regulate Slug/E-cadherin axis in oncogenic K-ras-expressing non-small cell lung carcinoma (NSCLC) cells, and (ii) the effect of aspirin in modulating the same. The migratory behaviour of NSCLC cell line A549 were deciphered by wound healing assay. Further assessment of the molecular mechanisms was done by western blotting, RT-PCR, confocal microscopy, chromatin immunoprecipitation and small interfering RNA (siRNA)-mediated gene silencing. Here we report that in oncogenic K-ras-expressing A549 cells, Ras/ERK downstream Elk-1 forms p-Elk-1-p300 complex that being directly recruited to SLUG promoter acetylates the same to ensure p65NFκB binding for transcriptional up-regulation of Slug, a transcriptional repressor of E-cadherin. Aspirin inhibits EMT and deceler...Continue Reading

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Citations

Jun 2, 2018·Medicinal Research Reviews·Hui HuaYangfu Jiang
Jun 16, 2016·Clinical Chemistry and Laboratory Medicine : CCLM·Ting-Juan ZhangJun Qian
May 1, 2019·Journal of Cancer Research and Clinical Oncology·Xiao ZhangXiaobo Li
Feb 1, 2019·Oncogene·Yifat Bar-Zakay RosenfeldJoel K Yisraeli
Sep 25, 2020·Cellular and Molecular Gastroenterology and Hepatology·Karen DunbarFarhat V N Din

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Methods Mentioned

BETA
transfection
ChIP
immunoprecipitation
nuclear translocation
acetylation
co-immunoprecipitation
histone acetylation
PCR

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