BAY 11-7082, An Anti-inflammatory Drug Attenuates Metastasis Potential Of Pak1 Over Expressing Cells By Modulating Pak1-NF-κB-p65?fibronectin Signaling Network | 25061
Journal of Cancer Science & Therapy
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p21-activated kinase 1 (Pak1) - a serine/threonine kinase, is a well-known regulator of cytoskeletal remodelling, cell motility,
cell proliferation, and cell survival, which can induce phosphorylation and activation of NF-κB, that can accelerate growth
and survival of cells. Our previous study have implicated that Pak1 by itself can have an oncogenic role in pancreatic cancer
through Pak1-NF-kappaB-p65?fibronectin pathway. Hence agents blocking downstream target of Pak1, namely NF-κB and
its activation, may reduce the invasiveness of pancreatic cancer. To test this hypothesis, we used BAY 11-7082 a known NF-κB
inhibitor and an anti inflammatory drug for the study. In the present study, we found BAY 11-7082 inhibited migration and
invasive capability of Pak1 over expressing pancreatic cell lines through blocking p65 NF-κB- Fibronectin pathway. We also
observed reduced fibronectin promoter activity on BAY 11-7082 treatment. Thus, the inactivation of NF-κB pathway, downregulated
fibronectin expression and reduces the metastasis potential of Pak1 over expressing pancreatic cancer, indicating
targeting Pak1-NF-kappaB-p65?fibronectin pathway might be an efficient treatment modality for pancreatic cancer patients.
SankarJagadeeshan is a graduate in Biotechnology, Chemistry and Zoology from University of Kerala and a post graduate in Biotechnology from Vellore Institute of
Technology, VIT University,Tamil Nadu. He has seven years of research experience in molecular oncology, translational biology, nanomedicine and drug delivery as
well as identification of novel drugs for cancer therapy. He had worked in premier institute of India viz., Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram,
Kerala and Indian Institute of Technology Madras, Tamil Nadu as research fellow. He has published nine papers in the field of microbiology, medicinal chemistry
and oncology and has two book chapters to his account. Currently he is a research scholar in Department of Genetics in University of Madras working on the role
of p21 activated kinase 1 in progression, metastasis, drug resistance and angiogenesis during pancreatic carcinogenesis.
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