Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers
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 a...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/11/2994 |
| _version_ | 1797510798679998464 |
|---|---|
| author | Mi-Hyeon You Woo Kyung Lee Meihua Jin Dong Eun Song Sheue-yann Cheng Tae Yong Kim Won Bae Kim Min Ji Jeon Won Gu Kim |
| author_facet | Mi-Hyeon You Woo Kyung Lee Meihua Jin Dong Eun Song Sheue-yann Cheng Tae Yong Kim Won Bae Kim Min Ji Jeon Won Gu Kim |
| author_sort | Mi-Hyeon You |
| collection | DOAJ |
| description | 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 β-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. |
| first_indexed | 2024-03-10T05:37:25Z |
| format | Article |
| id | doaj.art-7d14c5ee76f3475d887debc1f60cb4d3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:25Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7d14c5ee76f3475d887debc1f60cb4d32023-11-22T22:49:48ZengMDPI AGCells2073-44092021-11-011011299410.3390/cells10112994Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell MarkersMi-Hyeon You0Woo Kyung Lee1Meihua Jin2Dong Eun Song3Sheue-yann Cheng4Tae Yong Kim5Won Bae Kim6Min Ji Jeon7Won Gu Kim8Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaThe 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 β-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.https://www.mdpi.com/2073-4409/10/11/2994<i>DAPK1</i>thyroid cancerneoplastic stem cellstumor suppressor |
| spellingShingle | Mi-Hyeon You Woo Kyung Lee Meihua Jin Dong Eun Song Sheue-yann Cheng Tae Yong Kim Won Bae Kim Min Ji Jeon Won Gu Kim Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers Cells <i>DAPK1</i> thyroid cancer neoplastic stem cells tumor suppressor |
| title | Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers |
| title_full | Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers |
| title_fullStr | Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers |
| title_full_unstemmed | Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers |
| title_short | Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers |
| title_sort | death associated protein kinase 1 inhibits progression of thyroid cancer by regulating stem cell markers |
| topic | <i>DAPK1</i> thyroid cancer neoplastic stem cells tumor suppressor |
| url | https://www.mdpi.com/2073-4409/10/11/2994 |
| work_keys_str_mv | AT mihyeonyou deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT wookyunglee deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT meihuajin deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT dongeunsong deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT sheueyanncheng deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT taeyongkim deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT wonbaekim deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT minjijeon deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers AT wongukim deathassociatedproteinkinase1inhibitsprogressionofthyroidcancerbyregulatingstemcellmarkers |