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ITGA1 is a pre-malignant biomarker that promotes therapy resistance and metastatic potential in pancreatic cancer.


ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has single-digit 5-year survival rates at <7%. There is a dire need to improve pre-malignant detection methods and identify new therapeutic targets for abrogating PDAC progression. To this end, we mined our previously published pseudopodium-enriched (PDE) protein/phosphoprotein datasets to identify novel PDAC-specific biomarkers and/or therapeutic targets. We discovered that integrin alpha 1 (ITGA1) is frequently upregulated in pancreatic cancers and associated precursor lesions. Expression of ITGA1-specific collagens within the pancreatic cancer microenvironment significantly correlates with indicators of poor patient prognosis, and depleting ITGA1 from PDAC cells revealed that it is required for collagen-induced tumorigenic potential. Notably, collagen/ITGA1 signaling promotes the survival of ALDH1-positive stem-like cells and cooperates with TGF? to drive gemcitabine resistance. Finally, we report that ITGA1 is required for TGF?/collagen-induced EMT and metastasis. Our data suggest that ITGA1 is a new diagnostic biomarker and target that can be leveraged to improve patient outcomes.

SUBMITTER: Gharibi A 

PROVIDER: S-EPMC5577248 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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ITGA1 is a pre-malignant biomarker that promotes therapy resistance and metastatic potential in pancreatic cancer.

Gharibi Armen A   La Kim Sa S   Molnar Justin J   Brambilla Daniel D   Adamian Yvess Y   Hoover Malachia M   Hong Julie J   Lin Joy J   Wolfenden Laurelin L   Kelber Jonathan A JA  

Scientific reports 20170830 1


Pancreatic ductal adenocarcinoma (PDAC) has single-digit 5-year survival rates at <7%. There is a dire need to improve pre-malignant detection methods and identify new therapeutic targets for abrogating PDAC progression. To this end, we mined our previously published pseudopodium-enriched (PDE) protein/phosphoprotein datasets to identify novel PDAC-specific biomarkers and/or therapeutic targets. We discovered that integrin alpha 1 (ITGA1) is frequently upregulated in pancreatic cancers and assoc  ...[more]

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