Open AccessITGA1 is a pre-malignant biomarker that promotes therapy resistance and metastatic potential in pancreatic cancer
Author(s) -
Armen Gharibi,
Sa La Kim,
Justin Molnar,
Daniel Brambilla,
Yvess Adamian,
Malachia Hoover,
Julie Hong,
Joy Lin,
Laurelin Wolfenden,
Jonathan A. Kelber
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-09946-z
Subject(s) - pancreatic cancer , cancer research , biomarker , medicine , metastasis , gemcitabine , cancer , downregulation and upregulation , adenocarcinoma , oncology , biology , gene , biochemistry
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 TGFβ to drive gemcitabine resistance. Finally, we report that ITGA1 is required for TGFβ/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.