Death-Associated Protein Kinase 1 Inhibits Progression of Thyroid Cancer by Regulating Stem Cell Markers
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Updated: Oct 12, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Mi-Hyeon You1, Woo Kyung Lee2, Meihua Jin1
1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
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 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.
Insights
Death-associated protein kinase 1 (DAPK1) plays a crucial role in thyroid cancer progression. Inhibiting DAPK1 promotes cancer cell stemness and proliferation, while its overexpression suppresses these effects.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Metastatic reprogramming is key to cancer spread, yet its mechanisms remain unclear.
- The role of death-associated protein kinase 1 (DAPK1) in thyroid cancer progression requires further investigation.
Purpose of the Study:
- To elucidate the function of DAPK1 in thyroid cancer.
- To determine DAPK1's impact on cancer cell proliferation, invasion, and stemness.
Main Methods:
- DAPK1 was knocked down (KD) or overexpressed in human thyroid cancer cell lines (8505C, KTC-1, MDA-T32, BCPAP).
- Cell proliferation, colony formation, invasion, and tumorsphere formation assays were performed.
- Expression of stem cell markers (OCT4, Sox2, KLF4, Nanog) and β-catenin pathways were analyzed.
Main Results:
- DAPK1 KD increased proliferation, colony formation, and tumorsphere formation.
- DAPK1 overexpression inhibited cancer cell invasion and tumorsphere formation.
- DAPK1 modulated stem cell marker expression, potentially via β-catenin inhibition, correlating with advanced thyroid cancer stages.
Conclusions:
- DAPK1 acts as a tumor suppressor in thyroid cancer by inhibiting stemness and metastatic potential.
- DAPK1 expression levels are linked to thyroid cancer stage, stemness index, and patient survival.
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