Upregulated LAMA3 modulates proliferation, adhesion, migration and epithelial‑to‑mesenchymal transition of cholangiocarcinoma cells

        Cholangiocarcinoma (CCA), a bile duct cancer, is an aggressive cancer with poor prognosis. It is typically recognized by its dense extracellular matrix nature which associated with its malignancy behavior. Among various extracellular matrix proteins, laminin is the most potent inducer for CCA migration. Here by analyzing expression profiling of laminin gene family (11 genes) from four public transcriptome databases, we identified four laminin genes, namely, LAMA3, LAMA5, LAMB3, and LAMC2, as concordantly upregulated genes. Upregulation of these laminin genes were confirmed in CCA cell lines and tissues from Thai patients with LAMA3A upregulated in highest frequency (97%). Hierarchical clustering of low and high laminin signature groups revealed LAMA3 as the sole common differential expression genes (DEG) in all investigated datasets. Silencing LAMA3 revealed its roles in CCA cell proliferation, adhesion, and migration and epithelial mesenchymal transition. This study strengthens the importance of ECM homeostasis disruption in CCA malignancy and highlights, the potential of LAMA3 as the diagnostic marker and the therapeutic target to tackle the CCA stromal.

Reference

Islam K, Balasubramanian B, Venkatraman S, Thummarati P, Tunganuntarat J, Phueakphud N, et al. Upregulated LAMA3 modulates proliferation, adhesion, migration and epithelial to mesenchymal transition of cholangiocarcinoma cells. Sci Rep. 2023;13(1):22598.

DOI: 10.1038/s41598-023-48798-8