Proteomics identification of ITGB3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells

Yunlong Lei, Kai Huang, Cong Gao, Quek Lau, Hua Pan, Ke Xie, Jingyi Li, Rui Li, Tao Zhang, Na Xie, Huey Nai, Hong Wu, Qiang Dong, Xia Zhou, Edouard Nice, Canhua Huang, Yuquan Wei

Research output: Contribution to journalArticleResearchpeer-review

70 Citations (Scopus)

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and second in females worldwide. Unfortunately 40-50 of patients already have metastatic disease at presentation when prognosis is poor with a 5 year survival <10 . Reactive Oxygen Species (ROS) have been proposed to play a crucial role in tumor metastasis. We now show that higher levels of ROS accumulation are found in a colorectal cancer-derived metastatic cell line (SW620) compared to a cell line (SW480) derived from the primary lesion from the same patient. In addition, ROS accumulation can affect both the migratory and invasive capacity of SW480 and SW620 cells. To explore the molecular mechanism underlying ROS-induced migration and invasion in CRC, we have compared protein expression patterns between SW480 and SW620 cells using a 2-DE-based proteomics strategy. A total of 64 altered proteins were identified from MS/MS analysis. Cluster analysis revealed dysregulated expression of multiple redox regulative or ROS responsive proteins, implicating their functional roles in colorectal cancer metastasis. Molecular and pathological validation demonstrated that altered expression of PGAM1, GRB2, DJ-1, ITGB3, SOD-1 and STMN1 was closely correlated with the metastatic potential of CRC. Functional studies showed that ROS markedly up-regulated expression of ITGB3, which in turn promoted an aggressive phenotype in SW480 cells, with concomitant up-regulated expression of STMN1. In contrast, knockdown of ITGB3 expression could mitigate the migratory and invasive potential of SW620 or H2O2-treated SW480 cells, accompanied by down-regulated expression of STMN1. The function of ITGB3 was dependant on the surface expression of integrin alphaVbeta3 heterodimer. Furthermore, STMN1 expression and the PI3K-Akt-mTOR pathway were found to be involved in ROS-induced and ITGB3-mediated migration and invasion of colorectal cancer cells. Taken together, these studies suggest that ITGB3 plays an important role in ROS-induced migration and invasion in CRC.
Original languageEnglish
Article numberM110.005397
Number of pages16
JournalMolecular & Cellular Proteomics
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 2011

Cite this

Lei, Y., Huang, K., Gao, C., Lau, Q., Pan, H., Xie, K., Li, J., Li, R., Zhang, T., Xie, N., Nai, H., Wu, H., Dong, Q., Zhou, X., Nice, E., Huang, C., & Wei, Y. (2011). Proteomics identification of ITGB3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells. Molecular & Cellular Proteomics, 10(10 ), [M110.005397]. https://doi.org/10.1074/mcp.M110.005397