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Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers

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Abstract
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.
Author(s)
유미현이우경김미화송동은Sheue-yann Cheng김태용김원배전민지김원구
Issued Date
2021
Type
Article
Keyword
DAPK1 thyroid cancer neoplastic stem cells tumor suppressor
DOI
10.3390/cells10112994
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7539
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_7d14c5ee76f3475d887debc1f60cb4d3&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Death-Associated%20Protein%20Kinase%201%20Inhibits%20Progression%20of%20Thyroid%20Cancer%20by%20Regulating%20Stem%20Cell%20Markers&offset=0&pcAvailability=true
Publisher
CELLS
Location
스위스
Language
영어
ISSN
2073-4409
Citation Volume
10
Citation Number
11
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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