Fatty acid synthase contributes to epithelial-mesenchymal transition and invasion of salivary adenoid cystic carcinoma through PRRX1/Wnt/β-catenin pathway.
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.
['Zhang|Wei-Long|WL|', 'Wang|Sha-Sha|SS|0000-0002-1181-1672', 'Jiang|Ya-Ping|YP|', 'Liu|Yan|Y|', 'Yu|Xiang-Hua|XH|', 'Wu|Jing-Biao|JB|', 'Wang|Ke|K|', 'Pang|Xin|X|', 'Liao|Peng|P|', 'Liang|Xin-Hua|XH|0000-0001-7384-8748', 'Tang|Ya-Ling|YL|0000-0002-2010-3571']
D000818:Animals D017209:Apoptosis D003528:Carcinoma, Adenoid Cystic D002465:Cell Movement D049109:Cell Proliferation D058750:Epithelial-Mesenchymal Transition D064429:Fatty Acid Synthases D005260:Female D015972:Gene Expression Regulation, Neoplastic D020868:Gene Silencing D018398:Homeodomain Proteins D006801:Humans D008297:Male D008807:Mice, Inbred BALB C D008819:Mice, Nude D008875:Middle Aged D009361:Neoplasm Invasiveness D011379:Prognosis D012468:Salivary Gland Neoplasms D060449:Wnt Signaling Pathway D023041:Xenograft Model Antitumor Assays
fatty acid synthase epithelial-mesenchymal transition salivary adenoid cystic carcinoma PRRX1 Wnt/β-catenin