Role of PTEN and LKB1 in cellular metabolism: Implications in cancer cell biology

Abstract

Cellular metabolism is crucial for sustaining life, as it generates adenosine triphosphate (ATP) and provides essential building blocks for macromolecules. Recent research has expanded our understanding of metabolism, revealing its significant roles in cellular signaling networks related to immune responses, development, and aging. Cancer cells exhibit distinct metabolic characteristics due to reprogramming, particularly the Warburg effect, where they preferentially utilize glycolysis for energy production even in the presence of oxygen. This metabolic shift supports their uncontrolled proliferation and survival. This review explains the roles of two key tumor suppressor proteins, PTEN and LKB1, in regulating cellular metabolism and their implications for cancer biology. It aims to elucidate how these proteins influence metabolic pathways such as glycolysis and oxidative phosphorylation and to highlight their potential as therapeutic targets in cancer treatment. Dysregulation of LKB1 and PTEN due to mutations leads to enhanced glycolytic activity and metabolic reprogramming in cancer cells, contributing to tumorigenesis. LKB1 acts as a critical activator of AMP-activated protein kinase (AMPK), promoting energy homeostasis and regulating cellular metabolism under stress conditions. Conversely, PTEN functions as a negative regulator of the PI3K/AKT/mTOR signaling pathway, preventing uncontrolled cell growth. Understanding the mechanisms by which LKB1 and PTEN regulate cellular metabolism is essential for developing targeted anticancer therapies that exploit the unique metabolic vulnerabilities of cancer cells. By focusing on these pathways, researchers can identify new strategies to improve treatment efficacy while minimizing harm to normal tissues.