Cavin gene family and caveolae-related disorders: pathogenetic roles and possible mechanisms

Cavin基因家族与caveolae相关疾病:致病作用及可能机制

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Abstract

Cavins, in concert with caveolins, orchestrate the formation and function of caveolae-specialized invaginations of the plasma membrane involved in mechanotransduction, lipid homeostasis, and cell signaling. The Cavin family comprises four members: Cavins 1-3, which are broadly expressed, and Cavin4, which is muscle-specific. Disruption of Cavin function via genetic mutations, epigenetic silencing, or altered expression is linked to a spectrum of caveolae-related disorders, including lipodystrophy, muscular dystrophies, insulin resistance, and cancer. This review offers a comprehensive analysis of the physiological roles, pathophysiological implications, and therapeutic potential of cavins, with emphasis on their involvement in cancer, metabolic diseases, and muscle disorders, highlighting their value as biomarkers and molecular targets in precision medicine. Specifically, Cavin1 serves as the central structural and functional scaffold of caveolae, linking mechanoprotection, lipid metabolism, and ribosomal RNA transcription to cellular stress adaptation and disease pathogenesis, whereas Cavin2 modulates caveolae morphology and signaling, with emerging roles in insulin sensitivity and inflammatory regulation. Cavin3, in turn, is considered a dynamic regulator of caveolae turnover and signal integration, linking caveolar function to cell signaling, DNA damage responses, and tumor suppression. Finally, Cavin4 plays a critical role in muscle-specific caveolae organization, mechanotransduction, and hypertrophic signaling. In the context of tumorigenesis, cavins together represent promising therapeutic targets due to their capacity to induce apoptosis, inhibit cancer cell migration and invasion, and modulate inflammatory responses; however, their roles appear to be context-dependent, with expression patterns and functional outcomes varying across tissue types.

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