PINCH Translational Modifications Affect Chemotherapy Susceptibility on GBM Cells Depending on p53 Status
Garcia-Blanco A.1, Rahman A., Imbert F1., Tice C., Kalimuthusamy N., Langford D.1
1Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA
Gliomas are the most common adult CNS tumors and despite treatment efforts including surgery, radiation, and chemotherapy, essentially all low-grade gliomas progress to glioblastoma multiforme (GBM). Surgical resection is usually not possible and the recurrence rate of GBM is almost 100% after 9 months with a median survival of approximately 15 months due to its high capacity for invasion and resistance to therapy. Thus, improved therapeutic approaches are needed to decrease recurrence and prevent progression of astrocytoma into GBM. The PINCH protein is expressed in the mature CNS in neuropathological conditions, including Alzheimer’s Disease, HIV infection, or glioma. PINCH-mediated signaling involves cell migration, spreading, and survival pathways which are all critical events in cancer progression. In fact, increased PINCH expression is related to poor prognosis in colorectal, pancreatic and breast cancer. Our new data link PINCH expression with the anti-oncogenic gene p53, suggesting that the two proteins work in concert in progression to glioblastoma (GBM). p53 is mutated in approximately 80% of gliomas leading to p53 pathway deregulation that contributes to chemotherapy resistance. Our data show that PINCH is dramatically increased in brain cancers as a function of grade of malignancy. We also observed a PINCH post-translational modification linked to p53 mutation in glioma cell lines. Since PINCH expression levels and post-translational modifications are linked to vulnerability of GBM cells to therapeutic intervention, findings from these studies will provide valuable data for potential adjuvant therapies for GBM and possibly other cancers.
Email questions and comments about this abstract to alvaro.garcia@temple.edu.
