Article Dans Une Revue Cell Death and Disease Année : 2025

Atypical contribution of caspase-3 to melanoma cancer cell motility by regulation of coronin 1B activity

Hector Hernandez-Vargas

Résumé

Recent studies have unveiled unexpected connections between cell death and cell motility. While traditionally recognized for their pro-apoptotic roles, caspases have emerged as regulators of physiological processes beyond cell death, including cellular differentiation and motility. In some particularly aggressive cancers like melanoma, caspase-3, a prominent executioner caspase, is unexpectedly and inexplicably highly expressed. Here, we describe a novel non-apoptotic role for caspase-3 in melanoma cell motility. Through comprehensive molecular and cellular analyses, we demonstrate that caspase-3 is constitutively associated with the cytoskeleton and crucially regulates melanoma cell migration and invasion in vitro and in vivo . Mechanistically, caspase-3 interacts with and modulates the activity of coronin 1B, a key regulator of actin polymerization, thereby promoting melanoma cell motility, independently of its apoptotic protease function. Furthermore, we identify specificity protein 1 (SP1) as a transcriptional regulator of CASP3 expression, and show that its inhibition reduces caspase-3 expression and impairs melanoma cell migration. Overall, this study provides insights into the multifaceted roles of caspase-3 in cancer progression, highlighting its relevance as a novel target for anti-metastatic therapies.

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hal-05008919 , version 1 (10-10-2025)

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Kevin Berthenet, Serena Diazzi, Catherine Jamard, Kinga Stopa, Clara Gil, et al.. Atypical contribution of caspase-3 to melanoma cancer cell motility by regulation of coronin 1B activity. Cell Death and Disease, 2025, 16 (1), pp.690. ⟨10.1038/s41419-025-07952-y⟩. ⟨hal-05008919⟩
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