The role of fatty acid oxidation in metabolic crosstalk between tumor cells and associated factors in the microenvironment

Abstract

Metabolic reprogramming is a defining characteristic of cancer cells as they undergo multistage development. Cancer cells dynamically adjust their metabolism to aid their survival and to retain their malignant traits within the adverse tumour microenvironment (TME). Fatty acid oxidation (FAO) is a major source of cellular bioenergy, making it a key player in driving cancer cell growth. Over the past few years, an accumulating body of literature has shed light on the role of dysregulated FAO in cancer progression. Besides energy production, FAO also plays a protective role by mitigating lipotoxicity-induced cell death and preventing oxidative stress through NADPH production. Moreover, FAO is intricately linked with numerous critical signaling pathways, substantiating its importance as a pivotal metabolic adaptation in cancer cells. In the TME, various intrinsic and extrinsic factors continuously modulate the behaviour of cancer cells, including their metabolic attributes, such as the activation of FAO. Additionally, alterations in FAO within non-cancerous stromal cells also play a critical role in orchestrating the tumor progression. Despite the emerging recognition of FAO's significance in cancer biology, the precise molecular mechanisms underlying its dysregulation within the TME remain poorly understood. Given the pivotal role of FAO in bioenergetically priming the tumor progression, its aberrant regulation has become a focal point of cancer research, offering potential avenues for novel therapeutic strategies. This review provides an overview of recent advances in understanding how different microenvironmental factors modulate FAO to influence tumor progression.