Research Paper Volume 12, Issue 9 pp 7679—7693
Quantitative acetylome and phosphorylome analysis reveals Girdin affects pancreatic cancer progression through regulating Cortactin
- 1 Medical Center for Digestive Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China
received: October 13, 2019 ; accepted: February 25, 2020 ; published: May 5, 2020 ;https://doi.org/10.18632/aging.103032
How to Cite
Copyright © 2020 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The actin-binding protein Girdin is involved in a variety of cellular processes, including pancreatic cancer. The objective of this study is to explore the role and the mechanism of Girdin in pancreatic cancer by quantitative acetylome and phosphorylome analysis. We firstly found that Girdin was overexpressed in pancreatic cancer tissue and increased expression of Girdin was associated with tumor size and stage of patients with pancreatic cancer. We established the shRNA knockdown of Girdin in PANC-1 and Aspc-1 cells, and we found that shGirdin inhibited proliferation, migration and invasion, and promoted apoptosis. Subsequently, we identified and quantified 5,338 phosphorylated sites in 2,263 proteins that changed in response to Girdin knockdown, and identified a similar set of Girdin-responsive acetylome data as well. Additional data revealed that down-regulation of Girdin affected Cortactin phosphorylation and acetylation, suggesting Cortactin as an important regulatory target of Girdin. Moreover, we found that overexpression of Cortactin could rescue the effect of shGirdin on proliferation, apoptosism, migration and invasion of pancreatic cancer cells. In general, our results provided new insights into the mechanisms of Girdin function including cell proliferation, migration and invasion, and offer biomarker candidates for clinical evaluation of Girdin.