Clinical Evaluation of P21 Activated Kinase 1 (PAK1) Activation in Gliomas and Its Effect on Cell Proliferation

Abstract

Glioblastomas are the primary malignant tumors of brain tissues with poor prognosis and highly invasive phenotypes. Till now Ki-67 LI has emerged as a well-studied proliferation marker that aids in tumor grading, but labeling index alone cannot predict overall survival in gliomas. P21 activated kinase 1 (PAK1) – a serine/threonine kinase has been shown to function as downstream nodule for various oncogenic signaling pathways that promote neoplastic changes. This study is designed to evaluate the expression of PAK1 across various grades and its correlation with Ki-67 LI and overall survival rates among a total number of 140 clinical brain tumors of glioma patients. We also studied the activation status of phospho PAK1 in glioma tissues and established the role of PAK1 in proliferation of glioblatoma cell lines under γ-irradiation.This study provides molecular evidence signifying the role of PAK1 and its activation status in the progression of Gliomas to more aggressive phenotypes.

Keywords:

• PAK1
• glioma
• immunohistochemistry
• Ki-67 LI
• cell proliferation
• γ-irradiation

Acknowledgements

The authors thank the Management and Prof. S. P. Thyagarajan, Dean (Research), Sri Ramachandra Institute of Higher Education and Research (SRIHER) for infrastructural facilities, support and encouragement.

Ethical approval

The study was approved by the Institutional Ethical Committee (IEC) of Sri Ramachandra Institute of Higher Education and Research.

Disclosure statement

The authors declare no conflicts of interest.

Authors’ contributions

Study concept and design: GV and RSK; scientific guidance: DP, RSK and GV; data collection: AV, AB, RK, LDC, SM, DP, KG and VKV; manuscript preparation: VKV and GV; manuscript review: all authors.

Additional information

Funding

GV, KG and DP acknowledge the funding support from Department of Biotechnology, Govt. of India [vide sanction no., BT/PR/5034/BRB/10/1057/2012]; GV acknowledges SERB, Govt. of India for partial support of the study [vide sanction no., EMR/2016/007529]. RSK and DMA acknowledge the funding for this project by the grant from Department of Science and Technology, Govt. of India [project grant INT/RUS/RSF/P-26] and The Russian Science Foundation [No. 19-44-02006].