PMID- 33593111
OWN - NLM
STAT- MEDLINE
DCOM- 20211105
LR  - 20220716
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 246
IP  - 11
DP  - 2021 Jun
TI  - WISP1 aggravates cell metastatic potential by abrogating TGF-beta-Smad2/3-dependent 
      epithelial-to-mesenchymal transition in laryngeal squamous cell carcinoma.
PG  - 1244-1252
LID - 10.1177/1535370221992703 [doi]
AB  - Laryngeal squamous cell cancer (LSCC) is a common carcinoma with high morbidity 
      and mortality. Metastasis constitutes the major cause of death and poor prognosis 
      among patients with LSCC. Recent evidence confirms critical function of 
      Wnt1-inducible signaling protein 1 (WISP1) in several cancers. However, its 
      contribution in LSCC metastasis remains unclear. Specimens of tumor tissues and 
      adjacent normal mucosa were collected from patients with LSCC. The mRNA and 
      protein levels were determined using quantitative real-time PCR and Western blot, 
      respectively. RNA interference was applied to silence the expression of WISP1 and 
      TGF-beta, and recombinant adenovirus was used to overexpress WISP1 in human LSCC 
      cell line TU212 cells. Cell invasion and migration were determined by transwell 
      assay. High expression of WISP1 was observed in LSCC tissues, especially in those 
      from metastatic groups. Ectopic expression of WISP1 enhanced invasion and 
      migration of TU212 cells. On the contrary, WISP1 knockdown reduced numbers of 
      invasive and migrated cells. Additionally, elevation of WISP1 depressed the 
      expression of epithelial marker E-cadherin and increased levels of mesenchymal 
      marker vimentin in TU212 cells, whereas WISP suppression yielded the opposite 
      effects. Further analysis corroborated that WISP1 overexpression enhanced 
      activation of TGF-beta-Smad signaling by increasing expression of TGF-beta1, p-Smad2, 
      and p-Smad3, which was abrogated following WISP1 down-regulation. Moreover, 
      TGF-beta1 exposure facilitated LSCC cell invasion and migration. Notably, blockage 
      of the TGF-beta-Smad pathway by si-TGF-beta overturned WISP-1-evoked 
      epithelial-to-mesenchymal transition (EMT), and subsequent cell invasion and 
      migration. These findings highlight the pro-metastatic function of WISP1 in LSCC 
      by regulating cell invasion and migration via TGF-beta-Smad-mediated EMT, supporting 
      a promising invention target for LSCC therapy.
FAU - Song, Dandan
AU  - Song D
AD  - Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital 
      of Zhengzhou University, Zhengzhou 450052, P.R. China.
FAU - Wang, Liang
AU  - Wang L
AUID- ORCID: 0000-0003-1555-7277
AD  - Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital 
      of Zhengzhou University, Zhengzhou 450052, P.R. China.
FAU - Su, Ke
AU  - Su K
AD  - Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital 
      of Zhengzhou University, Zhengzhou 450052, P.R. China.
FAU - Wu, Huanhuan
AU  - Wu H
AD  - Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital 
      of Zhengzhou University, Zhengzhou 450052, P.R. China.
FAU - Li, Junli
AU  - Li J
AD  - Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital 
      of Zhengzhou University, Zhengzhou 450052, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210216
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (CCN Intercellular Signaling Proteins)
RN  - 0 (CCN4 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Aged
MH  - CCN Intercellular Signaling Proteins/genetics/*metabolism
MH  - Cell Movement
MH  - Epithelial-Mesenchymal Transition/*physiology
MH  - Female
MH  - Humans
MH  - Laryngeal Neoplasms/metabolism/*pathology
MH  - Male
MH  - Middle Aged
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Smad2 Protein/metabolism
MH  - Smad3 Protein/metabolism
MH  - Squamous Cell Carcinoma of Head and Neck/metabolism/*pathology
MH  - Transforming Growth Factor beta/genetics/metabolism
PMC - PMC8371311
OTO - NOTNLM
OT  - Laryngeal squamous cell cancer
OT  - Wnt1-inducible signaling protein 1
OT  - epithelial-to-mesenchymal transition
OT  - invasion
OT  - migration
OT  - transforming growth factor-beta
COIS- DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2021/02/18 06:00
MHDA- 2021/11/06 06:00
PMCR- 2022/06/01
CRDT- 2021/02/17 05:36
PHST- 2021/02/18 06:00 [pubmed]
PHST- 2021/11/06 06:00 [medline]
PHST- 2021/02/17 05:36 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 10.1177_1535370221992703 [pii]
AID - 10.1177/1535370221992703 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2021 Jun;246(11):1244-1252. doi: 
      10.1177/1535370221992703. Epub 2021 Feb 16.