Effects of YAP1 and SFRP2 overexpression on the biological behavior of colorectal cancer cells and their molecular mechanisms

Background:Colorectal cancer (CRC) is one of the most common malignancies worldwide and has a high mortality rate. With the development of tumor molecular biology, more and more attention is being paid to the mechanisms of cell pathways in colorectal carcinogenesis, such as the Hippo/Yes-associated protein 1 (YAP1) and Wnt/β-catenin signaling pathways. The abnormal expression of YAP1 and β-catenin have been reported in CRC, and can lead to excessive cell proliferation, and eventually, tumor formation. Secreted frizzled-related protein 2 (SFRP2) levels have been found to be decreased in a variety of cancers, and SFRP2 is an antagonist that binds directly to Wnt signal. At present, the molecular basis of colorectal tumors is still not fully understood. In the present study, we sought to identify the molecular mechanisms underlying YAP1 and SFRP2 in the development of CRC.

Methods:We constructed CRC cell lines that stably overexpressed YAP1 and SFRP2 using lentivirus packaging and cell infection. The levels of expression of the proteins were evaluated by western blot and immunofluorescence assays. Protein complex immunoprecipitation (Co-IP) was used to detect the interaction between YAP1, SFRP2, and β-catenin. The functional roles of YAP1 and SFRP2 in CRC was determined by a Cell Counting Kit-8 (CCK8) proliferation assay and flow cytometric apoptosis assay.

Results:The data of the present study showed that the overexpression of SFRP2 promoted the expression of YAP1 and β-catenin protein, and the overexpression of YAP1 promoted the expression of β-catenin protein. YAP1 overexpression promoted cell proliferation, while SFRP2 overexpression inhibited cell proliferation and promoted cell apoptosis.

Conclusions:Our findings showed that the expression of YAP1, SFRP2, and β-catenin is correlated in CRC cells. The Hippo pathway and Wnt pathway interact with each other in the pathogenesis of CRC, and YAP1 and SFRP2 are involved in the formation and development of CRC.

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