Differential involvement of RalA and RalB in colorectal cancer
0301 basic medicine
Colon
Molecular Sequence Data
Rectum
3. Good health
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Cell Line, Tumor
Proto-Oncogene Proteins
Mutation
Commentary
ras Proteins
Animals
Humans
ral GTP-Binding Proteins
Amino Acid Sequence
Colorectal Neoplasms
Cell Proliferation
Signal Transduction
DOI:
10.4161/sgtp.19571
Publication Date:
2012-05-08T01:43:39Z
AUTHORS (2)
ABSTRACT
Mutationally activated K-Ras can utilize a multitude of downstream effector proteins to promote oncogenesis. While the Raf and phosphoinositol 3-kinase effector pathways are the best-studied and validated, recent studies have established the critical importance of Ral guanine nucleotide exchange factor (RalGEF) activation of the RalA and RalB small GTPases in cancer biology. Due to recent evidence that the RalGEF-Ral pathway is necessary for the tumorigenic and metastatic potential of KRAS mutant pancreatic ductal adenocarcinoma (PDAC) tumor cells, we investigated whether or not Ral signaling was necessary for KRAS mutant colorectal cancer (CRC) tumor cell growth. As in PDAC, we found upregulated RalA and RalB activation in CRC tumor cell lines and tumors. Surprisingly we found antagonistic roles for RalA and RalB in the regulation of CRC tumor cell anchorage-independent growth. This observation contrasts with PDAC, where RalA but not RalB is necessary for PDAC tumor cell anchorage-independent growth. Our results emphasize cancer cell type differences in Ral function and hence the need for distinct Ral targeted therapeutic approaches in the treatment of CRC vs. PDAC.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (25)
CITATIONS (29)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....