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LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways

Published:August 03, 2021DOI:https://doi.org/10.1016/j.jid.2021.07.163
      Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. LPCAT1, a lysophosphatidylcholine acyltransferase, takes a center stage in membrane lipid remodeling. LPCAT1 is elevated in several cancers and contributes to cancer development. However, its role and molecular mechanisms in cSCC remain to be elucidated. In this study, we found that LPCAT1 was upregulated in cSCC tissues and in cell lines. In vitro, loss-of-function and gain-of-function experiments demonstrated that LPCAT1 facilitated cSCC cell proliferation, protected cells against apoptosis, accelerated epithelial‒mesenchymal transition, and enhanced cell metastasis. Mechanistically, LPCAT1 regulated EGFR signaling. The oncogenic effect of LPCAT1 was mediated by EGFR/protein kinase B and EGFR/p38MAPK pathways in cSCC. Using the xenograft mouse model, we consolidated the results mentioned earlier. In conclusion, LPCAT1 contributed to cSCC progression through EGFR-mediated protein kinase B and p38MAPK signaling pathways. LPCAT1 may serve as a target for therapeutic intervention in cSCC.

      Abbreviations:

      Akt (protein kinase B), cSCC (cutaneous squamous cell carcinoma), EMT (epithelial‒mesenchymal transition), IHC (immunohistochemistry), MMP (matrix metalloproteinase), sh (short hairpin), siRNA (small interfering RNA)
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