2. Academic Validation
  3. Upregulated LAMA3 modulates proliferation, adhesion, migration and epithelial‑to‑mesenchymal transition of cholangiocarcinoma cells

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

  • Sci Rep. 2023 Dec 18;13(1):22598. doi: 10.1038/s41598-023-48798-8.
Kittiya Islam 1,  Brinda Balasubramanian 1,  Simran Venkatraman 2,  Parichut Thummarati 3,  Janpen Tunganuntarat 1,  Nut Phueakphud 1,  Phongthon Kanjanasirirat 4,  Tanawadee Khumpanied 4,  Pornparn Kongpracha 1,  Yingpinyapat Kittirat 5 6 7,  Rutaiwan Tohtong 1,  Tavan Janvilisri 1,  Patompon Wongtrakoongate 1 8,  Suparerk Borwornpinyo 4 9,  Nisana Namwat 5 6 10,  Tuangporn Suthiphongchai 11
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
  • 2 Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
  • 3 Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 4 Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
  • 5 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 6 Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 7 Department of Medical Sciences, Regional Medical Sciences Center 2, Ministry of Public Health, Phitsanulok, 65000, Thailand.
  • 8 Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
  • 9 Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
  • 10 Department of Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 11 Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. [email protected].
PMID: 38114514 DOI: 10.1038/s41598-023-48798-8
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.

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