| First Author | Ma H | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 3 | Pages | 793-806.e6 |
| PubMed ID | 31968254 | Mgi Jnum | J:287189 |
| Mgi Id | MGI:6415647 | Doi | 10.1016/j.celrep.2019.12.075 |
| Citation | Ma H, et al. (2020) Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation. Cell Rep 30(3):793-806.e6 |
| abstractText | Periostin is a multifunctional extracellular matrix protein involved in various inflammatory diseases and tumor metastasis; however, evidence regarding whether and how periostin actively contributes to inflammation-associated tumorigenesis remains elusive. Here, we demonstrate that periostin deficiency significantly inhibits the occurrence of colorectal cancer in azoxymethane/dextran sulfate sodium-treated mice and in Apc(Min/+) mice. Moreover, periostin deficiency attenuates the severity of colitis and reduces the proliferation of tumor cells. Mechanistically, stromal fibroblast-derived periostin activates FAK-Src kinases through integrin-mediated outside-in signaling, which results in the activation of YAP/TAZ and, subsequently, IL-6 expression in tumor cells. Conversely, IL-6 induces periostin expression in fibroblasts by activating STAT3, which ultimately facilitates colorectal tumor development. These findings provide the evidence that periostin promotes colorectal tumorigenesis, and identify periostin- and IL-6-mediated tumor-stroma interaction as a promising target for treating colitis-associated colorectal cancer. |
