CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion
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 control...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
Impact Journals LLC
2015
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745755/ |
| id |
pubmed-4745755 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-47457552016-02-23 CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion Zhou, Pengcheng Erfani, Sonia Liu, Zeyi Jia, Changhe Chen, Yecang Xu, Bingwei Deng, Xinyu Alfáro, Jose E. Chen, Li Napier, Dana Lu, Michael Huang, Jian-An Liu, Chunming Thibault, Olivier Segal, Rosalind Zhou, Binhua P. Kyprianou, Natasha Horbinski, Craig Yang, Xiuwei H. Research Paper 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. Impact Journals LLC 2015-08-13 /pmc/articles/PMC4745755/ /pubmed/26377974 Text en Copyright: © 2015 Zhou et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Zhou, Pengcheng Erfani, Sonia Liu, Zeyi Jia, Changhe Chen, Yecang Xu, Bingwei Deng, Xinyu Alfáro, Jose E. Chen, Li Napier, Dana Lu, Michael Huang, Jian-An Liu, Chunming Thibault, Olivier Segal, Rosalind Zhou, Binhua P. Kyprianou, Natasha Horbinski, Craig Yang, Xiuwei H. |
| spellingShingle |
Zhou, Pengcheng Erfani, Sonia Liu, Zeyi Jia, Changhe Chen, Yecang Xu, Bingwei Deng, Xinyu Alfáro, Jose E. Chen, Li Napier, Dana Lu, Michael Huang, Jian-An Liu, Chunming Thibault, Olivier Segal, Rosalind Zhou, Binhua P. Kyprianou, Natasha Horbinski, Craig Yang, Xiuwei H. CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion |
| author_facet |
Zhou, Pengcheng Erfani, Sonia Liu, Zeyi Jia, Changhe Chen, Yecang Xu, Bingwei Deng, Xinyu Alfáro, Jose E. Chen, Li Napier, Dana Lu, Michael Huang, Jian-An Liu, Chunming Thibault, Olivier Segal, Rosalind Zhou, Binhua P. Kyprianou, Natasha Horbinski, Craig Yang, Xiuwei H. |
| author_sort |
Zhou, Pengcheng |
| title |
CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion |
| title_short |
CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion |
| title_full |
CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion |
| title_fullStr |
CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion |
| title_full_unstemmed |
CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion |
| title_sort |
cd151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with egfr to drive tumor cell motility and invasion |
| description |
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. |
| publisher |
Impact Journals LLC |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745755/ |
| _version_ |
1613535551705579520 |