PMID- 35366053
OWN - NLM
STAT- MEDLINE
DCOM- 20220510
LR  - 20220716
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 26
IP  - 9
DP  - 2022 May
TI  - Vestigial-like family member 3 stimulates cell motility by inducing high-mobility 
      group AT-hook 2 expression in cancer cells.
PG  - 2686-2697
LID - 10.1111/jcmm.17279 [doi]
AB  - Vestigial-like family member 3 (VGLL3) is a cofactor for TEA domain transcription 
      factors (TEADs). Although VGLL3 is known to be highly expressed and stimulate 
      cell proliferation in mesenchymal cancer cells, its involvement in mesenchymal 
      phenotypes is largely unknown. In this study, we found that VGLL3 promotes 
      epithelial-to-mesenchymal transition (EMT)-like phenotypic changes. We found that 
      A549 human lung cancer cells stably expressing VGLL3 exhibit spindle-like 
      morphological changes, reduction in the epithelial marker E-cadherin and 
      induction of the mesenchymal marker Snail. Notably, VGLL3-expressing cells 
      exhibited enhanced motility. The DNA-binding protein high-mobility group AT-hook 
      2 (HMGA2) was found to be a target of the VGLL3-TEAD4 complex, and 
      HMGA2 knockdown repressed EMT-like phenotypic changes in VGLL3-expressing cells. 
      VGLL3-dependent phenotypic changes are involved in transforming growth factor-beta 
      (TGF-beta)-induced EMT progression. VGLL3 or HMGA2 knockdown repressed the motility 
      of the mesenchymal breast cancer MDA-MB-231 cells. Importantly, high levels of 
      VGLL3 expression were shown to have a positive correlation with poor prognosis in 
      various human cancers, such as breast, colon, ovarian, head and neck, pancreatic, 
      renal, gastric and cervical cancers. These results suggest that VGLL3 promotes 
      EMT-like cell motility by inducing HMGA2 expression and accelerates cancer 
      progression.
CI  - (c) 2022 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Hori, Naoto
AU  - Hori N
AD  - Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, 
      Chiba University, Chiba, Japan.
AD  - Department of Molecular Cardiovascular Pharmacology, Graduate School of 
      Pharmaceutical Sciences, Chiba University, Chiba, Japan.
FAU - Takakura, Yuki
AU  - Takakura Y
AD  - Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, 
      Chiba University, Chiba, Japan.
FAU - Sugino, Ayumi
AU  - Sugino A
AD  - Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, 
      Chiba University, Chiba, Japan.
FAU - Iwasawa, Shuto
AU  - Iwasawa S
AD  - Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, 
      Chiba University, Chiba, Japan.
FAU - Nomizo, Kota
AU  - Nomizo K
AD  - Department of Molecular Cardiovascular Pharmacology, Graduate School of 
      Pharmaceutical Sciences, Chiba University, Chiba, Japan.
FAU - Yamaguchi, Naoto
AU  - Yamaguchi N
AD  - Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, 
      Chiba University, Chiba, Japan.
FAU - Takano, Hiroyuki
AU  - Takano H
AD  - Department of Molecular Cardiovascular Pharmacology, Graduate School of 
      Pharmaceutical Sciences, Chiba University, Chiba, Japan.
FAU - Yamaguchi, Noritaka
AU  - Yamaguchi N
AUID- ORCID: 0000-0002-1202-2915
AD  - Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, 
      Chiba University, Chiba, Japan.
AD  - Department of Molecular Cardiovascular Pharmacology, Graduate School of 
      Pharmaceutical Sciences, Chiba University, Chiba, Japan.
LA  - eng
GR  - 19K22482/Grants-in-Aid for Challenging Research (Exploratory)/
GR  - 21K06543/Scientific Research (C)/
GR  - 21J20257/JSPS/
GR  - Japanese Ministry of Education, Culture, Sports, Science and Technology/
GR  - Takeda Science Foundation/
GR  - Foundation for Promotion of Cancer Research in Japan/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220402
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Family
MH  - *Neoplasms/genetics
MH  - *Signal Transduction/genetics
MH  - Snail Family Transcription Factors
MH  - Transcription Factors/genetics/metabolism
MH  - Transforming Growth Factor beta/metabolism
PMC - PMC9077286
OTO - NOTNLM
OT  - EMT
OT  - TEAD
OT  - TGF-beta
OT  - VGLL3
OT  - signal transduction
COIS- The authors declare that they have no conflicts of interest regarding the 
      contents of this article.
EDAT- 2022/04/03 06:00
MHDA- 2022/05/11 06:00
PMCR- 2022/05/01
CRDT- 2022/04/02 08:33
PHST- 2022/02/09 00:00 [revised]
PHST- 2021/11/10 00:00 [received]
PHST- 2022/03/03 00:00 [accepted]
PHST- 2022/04/03 06:00 [pubmed]
PHST- 2022/05/11 06:00 [medline]
PHST- 2022/04/02 08:33 [entrez]
PHST- 2022/05/01 00:00 [pmc-release]
AID - JCMM17279 [pii]
AID - 10.1111/jcmm.17279 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2022 May;26(9):2686-2697. doi: 10.1111/jcmm.17279. Epub 2022 Apr 
      2.