PMID- 34831219
OWN - NLM
STAT- MEDLINE
DCOM- 20211223
LR  - 20211223
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 10
IP  - 11
DP  - 2021 Nov 3
TI  - Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by 
      Regulating Stem Cell Markers.
LID - 10.3390/cells10112994 [doi]
LID - 2994
AB  - The activation of metastatic reprogramming is vital for cancer metastasis, but 
      little is known about its mechanism. This study investigated the potential role 
      of death-associated protein kinase 1 (DAPK1) in thyroid cancer progression. We 
      generated knockdown (KD) DAPK1 using siRNA or shRNA in 8505C and KTC-1 cell 
      lines, which we transiently or stably overexpressed in MDA-T32 and BCPAP cell 
      lines. DAPK1 KD in 8505C and KTC-1 cells significantly increased cell 
      proliferation and colony formation compared with controls. We observed 
      significant inhibition of cancer cell invasion in cells overexpressing DAPK1, but 
      the opposite effect in KD cells. Tumorsphere formation significantly increased 
      after inhibition of DAPK1 expression in 8505C cells and was significantly 
      suppressed in DAPK1-overexpressing MDA-T32 and BCPAP cells. DAPK1 overexpression 
      inhibited mRNA and protein levels of stem markers (OCT4, Sox2, KLF4, and Nanog). 
      Furthermore, the expression of these markers increased after KD of DAPK1 in 8505C 
      cells. Mechanistic studies suggest that DAPK1 may modulate the expression of stem 
      cell markers through the inhibition of beta-catenin pathways. These findings were 
      consistent with the public data and our thyroid tissue analysis, which showed 
      higher DAPK1 expression was associated with advanced-stage papillary thyroid 
      cancer with a higher stemness index and lower disease-free survival.
FAU - You, Mi-Hyeon
AU  - You MH
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Korea.
FAU - Lee, Woo Kyung
AU  - Lee WK
AUID- ORCID: 0000-0002-6737-3173
AD  - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer 
      Institute, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Jin, Meihua
AU  - Jin M
AUID- ORCID: 0000-0003-0196-631X
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Korea.
FAU - Song, Dong Eun
AU  - Song DE
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul 05505, Korea.
FAU - Cheng, Sheue-Yann
AU  - Cheng SY
AD  - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer 
      Institute, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Kim, Tae Yong
AU  - Kim TY
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Korea.
FAU - Kim, Won Bae
AU  - Kim WB
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Korea.
FAU - Jeon, Min Ji
AU  - Jeon MJ
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Korea.
FAU - Kim, Won Gu
AU  - Kim WG
AUID- ORCID: 0000-0002-8404-7759
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul 05505, Korea.
LA  - eng
GR  - 2020R1F1A1049312 and 2020R1I1A1A01063399/the National Research Foundation of 
      Korea (NRF) funded by the Ministry of Education/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211103
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RNA, Messenger)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.1 (Death-Associated Protein Kinases)
SB  - IM
MH  - Biomarkers, Tumor/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Death-Associated Protein Kinases/genetics/*metabolism
MH  - *Disease Progression
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Neoplastic Stem Cells/*pathology
MH  - RNA, Messenger/genetics/metabolism
MH  - Thyroid Cancer, Papillary/enzymology/genetics/pathology
MH  - Thyroid Neoplasms/*enzymology/genetics/*pathology
MH  - Treatment Outcome
MH  - beta Catenin/metabolism
PMC - PMC8616132
OTO - NOTNLM
OT  - DAPK1
OT  - neoplastic stem cells
OT  - thyroid cancer
OT  - tumor suppressor
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/28 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/11/03
CRDT- 2021/11/27 01:14
PHST- 2021/10/13 00:00 [received]
PHST- 2021/10/28 00:00 [revised]
PHST- 2021/11/02 00:00 [accepted]
PHST- 2021/11/27 01:14 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/11/03 00:00 [pmc-release]
AID - cells10112994 [pii]
AID - cells-10-02994 [pii]
AID - 10.3390/cells10112994 [doi]
PST - epublish
SO  - Cells. 2021 Nov 3;10(11):2994. doi: 10.3390/cells10112994.