MassIVE MSV000095228

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

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Description

Recent studies have unveiled unexpected connections between cell death and cell motility involving caspases, key regulators of apoptosis. 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 coronin1-B, 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. [doi:10.25345/C5R78612P] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Caspase-3, motility, Cytoskeleton, Coronin-1B, lamellipodia

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Principal Investigators:
(in alphabetical order) 		Gabriel ICHIM, Center for Research on Cancer of Lyon (CRCL) University of Lyon 28, rue Laennec, 69008, Lyon, FRANCE
Submitting User: fdelolme
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