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Fatty acid synthase contributes to epithelial-mesenchymal transition and invasion of salivary adenoid cystic carcinoma through PRRX1/Wnt/β-catenin pathway.

Abstract
Fatty acid synthase (FASN) has been shown to be selectively up-regulated in cancer cells to drive the development of cancer. However, the role and associated mechanism of FASN in regulating the malignant progression of salivary adenoid cystic carcinoma (SACC) still remains unclear. In this study, we demonstrated that FASN inhibition attenuated invasion, metastasis and EMT of SACC cells as well as the expression ofPRRX1, ZEB1, Twist, Slug and Snail, among which the level of PRRX1 changed the most obviously. Overexpression of PRRX1 restored migration and invasion in FASN knockdown cells, indicating that PRRX1 is an important downstream target of FASN signalling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by FASN silencing and restored by PRRX1 overexpression. In addition, FASN expression was positively associated with metastasis and poor prognosis of SACC patients as well as with the expression of PRRX1, cyclin D1 and c-Myc in SACC tissues. Our findings revealed that FASN in SACC progression may induce EMT in a PRRX1/Wnt/β-catenin dependent manner.
AuthorsWei-Long Zhang, Sha-Sha Wang, Ya-Ping Jiang, Yan Liu, Xiang-Hua Yu, Jing-Biao Wu, Ke Wang, Xin Pang, Peng Liao, Xin-Hua Liang, Ya-Ling Tang
JournalJournal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 19 Pg. 11465-11476 (10 2020) ISSN: 1582-4934 [Electronic] England
PMID32820613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Chemical References
  • Homeodomain Proteins
  • PRRX1 protein, human
  • Fatty Acid Synthases
Topics
  • Animals
  • Apoptosis (genetics)
  • Carcinoma, Adenoid Cystic (genetics, pathology)
  • Cell Movement (genetics)
  • Cell Proliferation (genetics)
  • Epithelial-Mesenchymal Transition (genetics)
  • Fatty Acid Synthases (metabolism)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Homeodomain Proteins (genetics, metabolism)
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Salivary Gland Neoplasms (genetics, pathology)
  • Wnt Signaling Pathway
  • Xenograft Model Antitumor Assays

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