Variable A-type lamin expression in Merkel cell carcinoma cell lines and its association with nuclear integrity

Cancer research · Merkel cell carcinoma

MCPyV-positive Merkel cell carcinoma cell lines exhibit significantly lower A-type lamin (LMNA) expression and higher B-type lamin (LMNB1/LMNB2) expression compared to MCPyV-negative cell lines, leading to altered nuclear integrity and increased nuclear envelope rupture.

Merkel cell carcinoma (MCC) is an aggressive type of neuro‑endocrine skin cancer that can be subdivided into Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative cases. The nuclear lamina, composed of A‑ and B‑type lamins, has been implicated in cancer progression and can be altered by viral infections. This study investigated A‑ and B‑type lamin expression in MCPyV-negative and MCPyV-positive MCC cell lines, evaluated in relation to MCPyV status using live‑cell imaging, qPCR, and Western blotting. MCPyV-positive MCC cells displayed markedly lower A‑type lamin and higher B‑type lamin expression at both protein and mRNA levels relative to MCPyV-negative cells. Nuclear envelope (NE) ruptures were reversible in MCPyV‑negative cells but led to cell death in MCPyV‑positive cells. Transfection of MCPyV-negative cells with small (sT) or large (LT) tumor antigens did not reduce A‑type lamin levels. These data suggest that differential lamin expression and altered NE integrity may contribute to the aggressive phenotype of MCC and provide insight into viral‑host interactions in this malignancy.

Altered lamin expression may compromise nuclear envelope integrity, increasing susceptibility to enzymatic damage and influencing cell death pathways. Understanding how MCPyV status modulates lamin levels could reveal novel therapeutic targets for the highly aggressive Merkel cell carcinoma, guiding future precision medicine approaches.

Evidence level: Állatkísérletes. Állatmodellben vizsgálták.

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