CD151-'3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion

Pengcheng Zhou, Sonia Erfani, Zeyi Liu, Changhe Jia, Yecang Chen, Bingwei Xu, Xinyu Deng, Jose E. Alfáro, Li Chen, Dana Napier, Michael Lu, Jian An Huang, Chunming Liu, Olivier Thibault, Rosalind Segal, Binhua P. Zhou, Natasha Kyprianou, Craig Horbinski, Xiuwei H. Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 '3β1 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 '3β1 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 '3 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-'3β1 integrin complexes as promising prognostic biomarkers and therapeutic targets for glioblastoma.

Original languageEnglish (US)
Pages (from-to)29675-29693
Number of pages19
JournalOncotarget
Volume6
Issue number30
DOIs
StatePublished - 2015

Keywords

  • A3 integrin
  • CD151
  • Cell invasion and motility
  • EGFR
  • Glioblastoma

ASJC Scopus subject areas

  • Oncology

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