CD151-α3β1 Integrin Complexes are Prognostic Markers of Glioblastoma and Cooperate with EGFR to Drive Tumor Cell Motility and Invasion

Authors

Pengcheng Zhou, Harvard Medical School
Sonia Erfani, University of KentuckyFollow
Zeyi Liu, University of Kentucky
Changhe Jia, University of Kentucky
Yecang Chen, University of Kentucky
Bingwei Xu, University of Kentucky
Xinyu Deng, University of Kentucky
Jose E. Alfáro, Harvard Medical School
Li Chen, University of KentuckyFollow
Dana L. Napier, University of KentuckyFollow
Michael Lu, Florida Atlantic University
Jian-An Huang, First Affiliated Hospital of Soochow University, China
Chunming Liu, University of KentuckyFollow
Olivier Thibault, University of KentuckyFollow
Rosalind Segal, Harvard Medical School
Binhua P. Zhou, University of KentuckyFollow
Natasha Kyprianou, University of KentuckyFollow
Craig Horbinski, University of KentuckyFollow
Xiuwei H. Yang, University of KentuckyFollow

Abstract

Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based cohort of 96 patient biopsies and TCGA dataset to evaluate the clinical significance of CD151 and α3β1 integrin. Functional and signaling analyses were also conducted to understand how these molecules promote the aggressiveness of glioblastoma at molecular and cellular levels. Results from our analyses showed that CD151 and α3 integrin were significantly elevated in glioblastomas at both protein and mRNA levels, and exhibited strong inverse correlation with patient survival (p < 0.006). These adhesion molecules also formed tight protein complexes and synergized with EGF/EGFR to accelerate tumor cell motility and invasion. Furthermore, disruption of such complexes enhanced the survival of tumor-bearing mice in a xenograft model, and impaired activation of FAK and small GTPases. Also, knockdown- or pharmacological agent-based attenuation of EGFR, FAK or Graf (ARHGAP26)/small GTPase-mediated pathways markedly mitigated the aggressiveness of glioblastoma cells. Collectively, our findings provide clinical, molecular and cellular evidence of CD151-α3β1 integrin complexes as promising prognostic biomarkers and therapeutic targets for glioblastoma.

Document Type

Article

Publication Date

10-6-2015

Notes/Citation Information

Published in Oncotarget, v. 6, no. 30, p. 29675-29693.

Copyright @ 2016 Impact Journals, LLC

Licensed under a Creative Commons Attribution 3.0 License.

Digital Object Identifier (DOI)

http://dx.doi.org/10.18632/oncotarget.4896

Funding Information

This study was supported in part through NIH COBRE/pilot project fund and a pilot project grant from American Cancer Society #IRG 85-001-25 to X.H.Y. C.H. was supported by the National Cancer Institute (K08CA155764) and this research was supported by the Biospecimen and Tissue Procurement Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558). R. Segal was supported by NIH P01-CA142536 grant.

Repository Citation

Zhou, Pengcheng; Erfani, Sonia; Liu, Zeyi; Jia, Changhe; Chen, Yecang; Xu, Bingwei; Deng, Xinyu; Alfáro, Jose E.; Chen, Li; Napier, Dana L.; Lu, Michael; Huang, Jian-An; Liu, Chunming; Thibault, Olivier; Segal, Rosalind; Zhou, Binhua P.; Kyprianou, Natasha; Horbinski, Craig; and Yang, Xiuwei H., "CD151-α3β1 Integrin Complexes are Prognostic Markers of Glioblastoma and Cooperate with EGFR to Drive Tumor Cell Motility and Invasion" (2015). Pharmacology and Nutritional Sciences Faculty Publications. 38.
https://uknowledge.uky.edu/pharmacol_facpub/38