Changes in c-src activity in a human colon cancer cell line during differentiation

Sovová,; Kučerová, Dana; Liskova, M; Šloncová, Eva; Tuháčková, Zdena

doi:10.3892/or.4.2.451

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“…Reduction in Src activity and increase in sucrase-isomaltase expression have been observed in post confluent Caco-2/15 cells ( Seltana et al, 2013 ). Furthermore, it has been shown that differentiation of HT29 cells is accompanied by decreased kinase activity of Src ( Park et al, 1993 ; Sovova et al, 1997 ). Treatment of the cells was started at −2 days of confluence (80% confluence) and continued for 5 days and the cells were analyzed for the expression of sucrase-isomaltase (SI) and dipeptidyl peptidase IV (DPPIV), two well characterized terminal differentiation markers for absorptive cells ( Beaulieu et al, 1989 ; Beaulieu and Quaroni, 1991 ; Darmoul et al, 1992 ), and mucin 2 (MUC2) and trefoil factor 3 (TFF3) as specific markers for goblet cells ( Kim and Ho, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1

Fallah

Beaulieu

2021

Biology Open

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Intestinal cell lineage differentiation is a tightly regulated mechanism that involves several intracellular signaling pathways affecting the expression of a variety of transcription factors, which ultimately regulate cell specific gene expression. Absorptive and goblet cells are the two main epithelial cell types of the intestine. Previous studies from our group using an shRNA knockdown approach have shown that YAP1, one of the main Hippo pathway effectors, inhibits the differentiation of these two cell types. In the present study, we show that YAP1 activity is regulated by Src family kinases (SFKs) in these cells. Inhibition of SFKs led to a sharp reduction in YAP1 expression at the protein level, an increase in CDX2 and the P1 forms of HNF4α and of absorptive and goblet cell differentiation specific markers. Interestingly, in Caco-2/15 cells which express both YAP1 and its paralog TAZ, TAZ was not reduced by the inhibition of SFKs and its specific knockdown rather impaired absorptive cell differentiation indicating that YAP1 and TAZ are not always interchangeable for regulating cell functions.

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