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 |
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6Nju | Intestine - Large Intestine - Colon - Distal dysplasia - high grade |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
B6.129-Postntm1Jmol | Intestine - Large Intestine - Colon - Distal dysplasia - high grade |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
C57BL/6Nju | Intestine - Large Intestine - Colon - Distal dysplasia - low grade |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
B6.129-Postntm1Jmol | Intestine - Large Intestine - Colon - Distal dysplasia - low grade |
|
Intestine - Large Intestine - Colon - Distal |
100 |
|
B6.129-Postntm1Jmol | Intestine - Large Intestine - Colon - Distal lesion |
|
Intestine - Large Intestine - Colon - Distal |
observed - 80 |
|
B6.129-Postntm1Jmol | Intestine - Large Intestine - Colon - Distal tumor |
|
Intestine - Large Intestine - Colon - Distal |
observed |
|
C57BL/6Nju | Intestine - Large Intestine - Colon tumor |
|
Intestine - Large Intestine - Colon |
observed - 100 |
|
B6.129-Postntm1Jmol | Intestine - Large Intestine - Colon tumor |
|
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 |
|
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 |
|
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 |