GRB2 is traditionally thought of as an adaptor protein that links receptor tyrosine kinases to the RAS-MAPK pathway (Figure 1). It however also interacts with cytosolic tyrosine kinases such as FAK (PTK2). It has been implicated in the oncogenesis of solid tumours such as bladder and breast cancer. It also plays a role in cellular processes highly relevant to metastasis such as loss of cell adhesion (and concomitant resistance to apoptosis (anoikis resistance)), extracellular remodelling, cell motility, and tumour angiogenesis . There is limited knowledge of its role in pancreatic cancer.
|Figure 1: GRB2 is an adaptor protein. Credit: Kevin Marks. No changes were made. Creative Commons Attribution 2.0 Generic (CC BY 2.0).|
A new study has found that GRB2 is the target of a microRNA downregulated in pancreatic cancer (miR-329) . Re-introduction of miR-329 in pancreatic cancer cell lines resulted in reduced proliferation, reduced anchorage independent growth, and reduced tumour volume in mouse xenograft models. Furthermore ectopic expression of GRB2 and miR-329 together restored the wild-type cell line attributes suggesting miR-329’s oncosuppressive functions are mainly mediated by GRB2 in pancreatic cancer cells. Moving forward preclinical studies are planned using RNA interference to reduce GRB2 expression in models of pancreatic cancer .
- Giubellino, Alessio, Terrence R Burke, and Donald P Bottaro. ‘Grb2 Signaling in Cell Motility and Cancer’. Expert Opinion on Therapeutic Targets 12, no. 8 (August 2008): 1021–33. doi:10.1517/1472822.214.171.1241.
- Wang, Xinjing, Xiongxiong Lu, Tian Zhang, Chenlei Wen, Minmin Shi, Xiaomei Tang, Hao Chen, et al. ‘Mir-329 Restricts Tumor Growth by Targeting grb2 in Pancreatic Cancer’. Oncotarget, 14 February 2016. doi:10.18632/oncotarget.7375.
- ‘Bio-Path Holdings Announces Pancreatic Cancer Research Collaboration with Leading Oncology Institution | Business Wire’. Accessed 8 March 2016. http://www.businesswire.com/news/home/20160308005180/en/Bio-Path-Holdings-Announces-Pancreatic-Cancer-Research-Collaboration.