YAP, a novel target regulates F-actin rearrangement-associated CAFs transformation and promotes colorectal cancer cell progression
Issued Date
2022-11-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-85139282838
Pubmed ID
36271545
Journal Title
Biomedicine and Pharmacotherapy
Volume
155
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.155 (2022)
Suggested Citation
Naktubtim C., Payuhakrit W., Uttarawichien T., Hassametto A., Suwannalert P. YAP, a novel target regulates F-actin rearrangement-associated CAFs transformation and promotes colorectal cancer cell progression. Biomedicine and Pharmacotherapy Vol.155 (2022). doi:10.1016/j.biopha.2022.113757 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86826
Title
YAP, a novel target regulates F-actin rearrangement-associated CAFs transformation and promotes colorectal cancer cell progression
Author's Affiliation
Other Contributor(s)
Abstract
Colorectal cancer (CRC) progression is strongly influenced by the tumor microenvironment (TME) in which cancer-associated fibroblasts (CAFs) are the major components influencing CRC growth and progression. The present study aimed to investigate the effect of YAP on F-actin arrangement in CAF transformation and the possibility of using YAP as a target for inhibiting CRC growth and progression. Conditioned media were collected from direct interaction between CRC cells and fibroblasts. CAF markers were investigated by flow cytometry, western blot analysis, and immunofluorescence assay in CM-treated fibroblasts. Promoting the CRC progression of conditioned media was determined in CRC cells by using MTT assay, fluorescence assay, wound healing assay, transwell migration assay, and tubulogenesis. The results showed that the conditioned media induced the expression of CAF markers associated with the central rearrangement of F-actin in colon fibroblasts, upregulating and promoting the nuclear translocation of YAP. The conditioned media also significantly promoted the proliferation, migration, invasion, and angiogenesis of CRC cells. Interestingly, Verteporfin, a YAP inhibitor during cocultivation, abolished the conversion of CAFs and inhibited proliferation, migration, invasion, and angiogenesis in CRC cells. Moreover, bioinformatics analysis was employed to determine the potential role of YAP as a prognostic marker in CRC patients from databases. The results suggested that YAP has higher expression in CRC patients and is associated with a poor prognosis. In conclusion, these findings demonstrate that YAP-related F-actin rearrangement may be a potential new target of combination therapy with a focus on targeting TME.