Insights into Structure and Function of Growth Arrest Specific 2 (GAS2)

Growth arrest specific 2 (GAS2) is a microfilament-associated protein, which is widely distributed in human tissues. It exerts a pivotal influence on various cellular processes, including cytoskeletal regulation, cell cycle progression, apoptosis, and senescence. GAS2 has a dual function in cancer cell growth: on the one hand, it enhances the sensitivity of cancer cells to chemoradiotherapy and prevents malignant transformation of normal cells; but on the other hand, it maintains the growth of cancer cells. GAS2 regulates the cellular activity of Calpain-2, a calcium-dependent protease, by acting as an endogenous inhibitor of the enzyme. The N-terminus of GAS2 binds to Calpain-2, while its C-terminus acts as an inhibitor of the protease activity of Calpain-2. The functional outcome of GAS2 is highly dependent on the specific substrates of Calpain-2 and cellular environment, particularly within tumor cells. Despite garnering increasing attention and a growing body of related research, a systematic review of GAS2 remains absent. This review aims to elucidate the structural and functional aspects of GAS2, with a particular emphasis on its implications in cancer. By comprehensively detailing its role and research progress in malignancies, this review endeavors to furnish novel insights for enhancing the therapeutic strategies against diseases, particularly cancers.