PMID- 33420975
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20211221
IS  - 1573-6881 (Electronic)
IS  - 0145-479X (Linking)
VI  - 53
IP  - 1
DP  - 2021 Feb
TI  - KLK11 acts as a tumor-inhibitor in laryngeal squamous cell carcinoma through the 
      inactivation of Akt/Wnt/beta-catenin signaling.
PG  - 85-96
LID - 10.1007/s10863-020-09870-4 [doi]
AB  - Kallikrein-associated peptidase 11 (KLK11) has emerged as a key tumor-associated 
      protein that is implicated in a wide spectrum of tumor types. However, the 
      detailed involvement of KLK11 in laryngeal squamous cell carcinoma (LSCC) has not 
      been well studied. The aims of our work were to evaluate whether KLK11 plays a 
      role in LSCC. We found that both the mRNA and protein expression of KLK11 were 
      significantly lower in LSCC tissues than in normal tissues. Low expression of 
      KLK11 was also observed in LSCC cell lines, and the up-regulation of KLK11 caused 
      a significant inhibitory effect on the proliferation, colony formation and 
      invasion of LSCC cells. On the contrary, the knockdown of KLK11 markedly 
      accelerated the proliferative and invasive abilities of LSCC cells. Molecular 
      mechanism research revealed that KLK11 overexpression decreased the 
      phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) and down-regulated the 
      expression of active beta-catenin, leading to the inactivation of Wnt/beta-catenin 
      signaling in LSCC cells. Furthermore, GSK-3beta inhibition markedly abrogated the 
      KLK11-mediated suppressive effect on Wnt/beta-catenin signaling. Notably, the 
      reactivation of Wnt/beta-catenin partially reversed KLK11-mediated tumor-inhibition 
      effect in LSCC. In addition, the xenograft tumor assay demonstrated that the 
      up-regulation of KLK11 retarded tumor formation and the growth of LSCC cells in 
      vivo. Taken together, the findings of our work demonstrate that KLK11 exerts a 
      tumor-inhibition role in LSCC by down-regulating Wnt/beta-catenin signaling. Our 
      work highlights a pivotal role of KLK11 in LSCC progression and suggests it as an 
      attractive anticancer target for LSCC treatment.
FAU - Zhao, Ruimin
AU  - Zhao R
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
FAU - Wang, Shiyang
AU  - Wang S
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
FAU - Liu, Junsong
AU  - Liu J
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
FAU - Xu, Chongwen
AU  - Xu C
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
FAU - Zhang, Shaoqiang
AU  - Zhang S
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
FAU - Shao, Yuan
AU  - Shao Y
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
FAU - Duan, Xiaoyi
AU  - Duan X
AUID- ORCID: 0000-0002-5364-9482
AD  - Department of Medical Image and Nuclear Medicine, The First Affiliated Hospital 
      of Xi'an Jiaotong University, No.277 Yanta West Road, Xi'an, 710061, Shaanxi 
      Province, China. duanxyxjtu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20210109
PL  - United States
TA  - J Bioenerg Biomembr
JT  - Journal of bioenergetics and biomembranes
JID - 7701859
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (beta Catenin)
RN  - 0 (trypsin-like serine protease)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Animals
MH  - Head and Neck Neoplasms/genetics/*metabolism/pathology
MH  - Heterografts
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Serine Endopeptidases/*metabolism
MH  - Squamous Cell Carcinoma of Head and Neck/genetics/*metabolism/pathology
MH  - *Wnt Signaling Pathway
MH  - beta Catenin/*metabolism
OTO - NOTNLM
OT  - GSK-3beta
OT  - KLK11
OT  - LSCC
OT  - Wnt
EDAT- 2021/01/10 06:00
MHDA- 2021/12/22 06:00
CRDT- 2021/01/09 12:07
PHST- 2020/10/18 00:00 [received]
PHST- 2020/12/29 00:00 [accepted]
PHST- 2021/01/10 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/01/09 12:07 [entrez]
AID - 10.1007/s10863-020-09870-4 [pii]
AID - 10.1007/s10863-020-09870-4 [doi]
PST - ppublish
SO  - J Bioenerg Biomembr. 2021 Feb;53(1):85-96. doi: 10.1007/s10863-020-09870-4. Epub 
      2021 Jan 9.