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Publications

Journal Article Review Ahead of print

PubMed: 41437263 DOI: 10.1080/14728222.2025.2608032

Sugars to signals: emerging roles of PAK1 in Re-wiring glucose metabolism in cancers.

Expert Opin Ther Targets

Authors: Prarthana Gopinath, Srikanth Swamy Swaroop B, Ganesh Venkatraman, Suresh Kumar Rayala

Affiliations

  • Molecular Oncology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
  • Molecular Oncology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India. Department of Human Genetics, Sri Ramachandra Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.
  • Department of Bio-Medical Sciences, School of Bio Sciences & Technology, Vellore Institute of Technology, Vellore, India.
  • Center for Sustainability, School of Interdisciplinary Sciences (sidis), Indian Institute of Technology Madras, Chennai, India.

Abstract

UNLABELLED

p21-activated kinase 1 (PAK1) is a critical serine/threonine kinase involved in regulating key cellular processes driving cancer progression. While PAK1 is well-known for its contributions to the hallmarks of cancer - such as sustained proliferation, evasion of apoptosis, and metastasis - emerging evidence highlights its pivotal role in cancer metabolism, particularly in orchestrating the Warburg effect.

AREAS COVERED

This review focuses on the multifaceted influence of PAK1 in metabolic reprogramming, emphasizing both its direct and indirect regulation of aerobic glycolysis, a hallmark metabolic adaptation in tumor cells. We explore how PAK1 modulates signaling pathways and metabolic enzymes to shift glucose metabolism toward glycolysis, supporting the biosynthetic and energetic demands of rapidly proliferating cancer cells. By bridging oncogenic signaling and metabolic remodeling, PAK1 acts as a central integrator that facilitates tumor growth and survival. Elucidating the mechanistic links between PAK1 and the Warburg effect unveils novel opportunities for targeted cancer therapies aimed at disrupting metabolic vulnerabilities.

EXPERT OPINION

An ideal biodegradable drug delivery system and an appropriately representative pre-clinical model exploiting the Warburg effect could enhance targeted delivery and therapeutic efficacy, and could help advance tumor targeted therapies in aggressive cancers like TNBC and pancreatic cancer.

MeSH

Cells, Neoplasms, Sugars, Drug Delivery Systems, Therapeutics, Protein Serine-Threonine Kinases