Targeting centromere protein M represses cell growth and mobility via inactivating AKT pathway but less affects BRAF...

Area of Science:

• Oncology
• Molecular Biology
• Dermatology

Background:

• Centromere protein M (CENPM) is implicated in oncogenesis and serves as a prognostic biomarker in various cancers.
• The role of CENPM in cutaneous melanoma, a common skin cancer, remains unclear.
• Understanding CENPM's function is crucial for developing targeted melanoma therapies.

Purpose of the Study:

• To investigate the effects of targeting CENPM on melanoma cell behavior, including proliferation, apoptosis, invasion, and migration.
• To determine CENPM's impact on BRAF inhibitor sensitivity and key signaling pathways (Wnt/β-catenin, AKT, P53) in melanoma.
• To analyze the clinical relevance of CENPM expression in cutaneous melanoma patients.

Main Methods:

• Melanoma cell lines (A375, SK-MEL-28) were transfected with CENPM siRNA (si-CENPM).
• Cellular functions and pathway modulation were assessed after si-CENPM transfection and treatment with BRAF inhibitors (dabrafenib, vemurafenib) and an AKT activator (740Y-P).
• Clinical data analysis was performed using the GEPIA public database to correlate CENPM expression with patient survival.

Main Results:

• si-CENPM significantly reduced melanoma cell proliferation, invasion, and migration while increasing apoptosis.
• si-CENPM decreased colony formation in A375 cells but not SK-MEL-28 cells.
• Targeting CENPM inactivated the AKT pathway with minimal effects on Wnt/β-catenin and P53 pathways; AKT activation partially reversed these effects.
• CENPM expression was upregulated in cutaneous melanoma patients and correlated with poorer overall survival.

Conclusions:

• Targeting CENPM suppresses cutaneous melanoma growth and migration, primarily through the inactivation of the AKT pathway.
• CENPM represents a potential therapeutic target for cutaneous melanoma.
• Upregulation of CENPM is a negative prognostic factor in cutaneous melanoma.