Back to Search
Start Over
Ubiquitin-binding associated protein 2 regulates KRAS activation and macropinocytosis in pancreatic cancer.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Sep; Vol. 34 (9), pp. 12024-12039. Date of Electronic Publication: 2020 Jul 21. - Publication Year :
- 2020
-
Abstract
- Macropinocytosis supports the metabolic requirement of RAS-transformed pancreatic ductal adenocarcinoma cells (PDACs). However, regulators of RAS-transformation (activation) that lead to macropinocytosis have not been identified. Herein, we report that UBAP2 (ubiquitin-binding associated protein 2), regulates the activation of KRAS and macropinocytosis in pancreatic cancer. We demonstrate that UBAP2 is highly expressed in both pancreatic cancer cell lines and tumor tissues of PDAC patients. The expression of UBAP2 is associated with poor overall survival in several cancers, including PDAC. Silencing UBAP2 decreases the levels of activated KRAS, and inhibits macropinocytosis, and tumor growth in vivo. Using a UBAP2-deletion construct, we demonstrate that the UBA-domain of UBAP2 is critical for the regulation of macropinocytosis and maintaining the levels of activated KRAS. In addition, UBAP2 regulates RAS downstream signaling and helps maintain RAS in the GTP-bound form. However, the exact mechanism by which UBAP2 regulates KRAS activation is unknown and needs further investigation. Thus, UBAP2 may be exploited as a potential therapeutic target to inhibit macropinocytosis and tumor growth in activated KRAS-driven cancers.<br /> (© 2020 Federation of American Societies for Experimental Biology.)
- Subjects :
- Carrier Proteins genetics
Cell Line, Tumor
Enzyme Activation
Gene Silencing
Humans
Pancreatic Neoplasms genetics
Pancreatic Neoplasms pathology
Protein Domains
Proto-Oncogene Proteins p21(ras) genetics
Carrier Proteins metabolism
Pancreatic Neoplasms metabolism
Pinocytosis
Proto-Oncogene Proteins p21(ras) metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 34
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 32692445
- Full Text :
- https://doi.org/10.1096/fj.201902826RR