Reference SummaryMa H, Cell Rep 2020 Jan 21;30(3):793-806.e6

Title

 Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation.

Authors

 Ma H; Wang J; Zhao X; Wu T; Huang Z; Chen D; Liu Y; Ouyang G

Journal

 Cell Rep

Volume

 30

Issue

 3

Year

 2020

Pages

 793-806.e6

Abstract

 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.

Links

 J:287189 – MGI References
31968254 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6Nju Intestine - Large Intestine - Colon - Distal dysplasia - high grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon - Distal

100
B6.129-Postntm1Jmol Intestine - Large Intestine - Colon - Distal dysplasia - high grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon - Distal

100
C57BL/6Nju Intestine - Large Intestine - Colon - Distal dysplasia - low grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon - Distal

100
B6.129-Postntm1Jmol Intestine - Large Intestine - Colon - Distal dysplasia - low grade
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon - Distal

100
B6.129-Postntm1Jmol Intestine - Large Intestine - Colon - Distal lesion
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon - Distal

observed - 80
B6.129-Postntm1Jmol Intestine - Large Intestine - Colon - Distal tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon - Distal

observed
C57BL/6Nju Intestine - Large Intestine - Colon tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

observed - 100
B6.129-Postntm1Jmol Intestine - Large Intestine - Colon tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Colon

observed - 93.75
C57BL/6Nju Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

observed
C57BL/6Nju Intestine - Large Intestine - Rectum tumor Intestine - Large Intestine - Rectum

0
C57BL/6Nju Intestine - Large Intestine - Rectum tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Rectum

observed
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Rectum tumor Intestine - Large Intestine - Rectum

observed
B6.129-Postntm1Jmol Intestine - Large Intestine - Rectum tumor
  • dextran sulfate sodium (DSS)
  • azoxymethane (AOM)
 Intestine - Large Intestine - Rectum

observed
C57BL/6J-ApcMin/+ Intestine - Large Intestine tumor Intestine - Large Intestine

77.78
C57BL/6-ApcMin/+ Postntm1Jmol Intestine - Large Intestine tumor Intestine - Large Intestine

11.11
C57BL/6Nju Intestine - Large Intestine tumor Intestine - Large Intestine

0
B6.129-Postntm1Jmol Intestine - Large Intestine tumor Intestine - Large Intestine

0
C57BL/6J-ApcMin/+ Intestine - Small Intestine tumor Intestine - Small Intestine

100
C57BL/6-ApcMin/+ Postntm1Jmol Intestine - Small Intestine tumor Intestine - Small Intestine

100
C57BL/6Nju Intestine - Small Intestine tumor Intestine - Small Intestine

0
B6.129-Postntm1Jmol Intestine - Small Intestine tumor Intestine - Small Intestine

0