MiR-7a is an important mediator in Fas-associated protein with death domain (FADD)-regulated expression of focal adhesion kinase (FAK).
Fas-associated protein with death domain (FADD), a classical adaptor protein mediating apoptotic stimuli-induced cell death, has been reported to engage in several non-apoptotic processes such as T cell and cardiac development and tumorigenesis. Recently, there are several reports about the FADD's involvement in cell migration, however the underlying mechanism remains elusive. Here, we present a new finding that FADD could regulate the expression of FAK, a non-receptor protein tyrosine kinase overexpressed in many cancers, and played an important role in cell migration in murine MEF and melanoma cells with different metastatic potential, B16F10 and B16F1. Moreover, miR-7a, a tumor suppressor which prohibits cell migration and invasion, was up-regulated in FADD-deficient cells. And FAK was verified to be the direct target gene of miR-7a in B16F10 cells. Furthermore, we demonstrate that miR-7a was a necessary mediator in FADD-regulated FAK expression. In contrast to its classical apoptotic role, FADD interference could reduce the rate of cell migration, which could be rescued by inhibiting miR-7a expression. Taken together, our data provide a novel explanation regarding how FADD regulates cell migration in murine melanoma cells.
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.
Yingting
Y
Liu
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.
Hongen
H
Cui
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.
Xianjie
X
Huang
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.
Bo
B
Zhu
Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, China.
Shengwen
S
Guan
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.
Wei
W
Cheng
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.
Yueyang
Y
Lai
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.
Xiaoxin
X
Zhang
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China.|The State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210017, China.|The State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210008, China.
Zi-Chun
ZC
Hua
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D053200:Fas-Associated Death Domain Protein / Q000502:physiology*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology
C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; C549243:MIRN7 microRNA, mouse; D035683:MicroRNAs; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse
FADD; FAK; melanoma; miR-7a; migration