Upregulated LAMA3 modulates proliferation, adhesion, migration and epithelial‑to‑mesenchymal transition of cholangiocarcinoma cells
Issued Date
2023-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85180180675
Pubmed ID
38114514
Journal Title
Scientific Reports
Volume
13
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.13 No.1 (2023)
Suggested Citation
Islam K., Balasubramanian B., Venkatraman S., Thummarati P., Tunganuntarat J., Phueakphud N., Kanjanasirirat P., Khumpanied T., Kongpracha P., Kittirat Y., Tohtong R., Janvilisri T., Wongtrakoongate P., Borwornpinyo S., Namwat N., Suthiphongchai T. Upregulated LAMA3 modulates proliferation, adhesion, migration and epithelial‑to‑mesenchymal transition of cholangiocarcinoma cells. Scientific Reports Vol.13 No.1 (2023). doi:10.1038/s41598-023-48798-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/95925
Title
Upregulated LAMA3 modulates proliferation, adhesion, migration and epithelial‑to‑mesenchymal transition of cholangiocarcinoma cells
Corresponding Author(s)
Other Contributor(s)
Abstract
A poor outcome for cholangiocarcinoma (CCA) patients is still a clinical challenge. CCA is typically recognized by the desmoplastic nature, which accounts for its malignancy. Among various extracellular matrix proteins, laminin is the most potent inducer for CCA migration. Herein, we accessed the expression profiles of laminin gene family and explored the significance of the key laminin subunit on CCA aggressiveness. Of all 11 laminin genes, LAMA3, LAMA5, LAMB3 and LAMC2 were concordantly upregulated based on the analysis of multiple public transcriptomic datasets and also overexpressed in Thai CCA cell lines and patient tissues in which LAMA3A upregulated in the highest frequency (97%) of the cases. Differential expression genes (DEGs) analysis of low and high laminin signature groups revealed LAMA3 as the sole common DEG in all investigated datasets. Restratifying CCA samples according to LAMA3 expression indicated the association of LAMA3 in the focal adhesion pathway. Silencing LAMA3 revealed that it plays important roles in CCA cell proliferation, adhesion, migration and epithelial-to-mesenchymal transition. Taken together, this research signifies the roles of dysregulated ECM homeostasis in CCA malignancy and highlights, for the first time, the potential usage of LAMA3 as the diagnostic biomarker and the therapeutic target to tackle the CCA stromal.