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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2023.3
- 수록면
- 285 - 293 (9page)
- DOI
- 10.1007/s13258-022-01351-9
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초록· 키워드
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Background Elevated expression of Dickkopf-1 (DKK1) is frequently observed in hepatocellular carcinoma (HCC) patients with poor clinical outcomes. Several reports indicating the functional involvement of DKK1 in HCC progression have suggested DKK1 as a promising therapeutic target for HCC.
Objective In this study, to develop an efficient way to target DKK1, we assessed the effect of CDK9 inhibitors on DKK1 expression linked to metastatic movement of HCC.
Methods The expression of DKK1 in CDK9 inhibitor-treated HCC cells was measured by western blot, ELISA and quantitative real-time reverse transcription PCR. Wound healing assay, migration assay, invasion assay and western blot were examined to evaluate the functional role of DKK1 in CDK9 inhibitors-treated HCC.
Results Inactivation of CDK9 either by a catalytic inhibitor being clinically evaluated or by a specific CDK9 protein degrader largely downregulated DKK1 expression at the transcript and protein levels. In addition, CDK9 inhibitors suppressed the migration and invasion of HCC cells. We observed that ectopic high expression of DKK1 at least partially reversed the defects in metastatic movement of HCC cells mediated by CDK9 inhibitors. We further discovered that the DKK1-nuclear β-catenin axis associated with the metastatic potential of HCC cells was impaired by CDK9 inhibitors.
Conclusion Taken together, our findings suggest that CDK9 inhibitors are potent tools to target DKK1, which can suppress the metastatic progression of HCC.
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