TP53INP1 Downregulation Activates a p73-Dependent DUSP10/ERK Signaling Pathway to Promote Metastasis of Hepatocellular Carcinoma
| Autor: | Ng, Kai-Yu, Chan, Lok-Hei, Chai, Stella, Tong, Man, Guan, Xin-Yuan, Lee, Nikki, Yuan, Yunfei, Xie, Dan, Lee, Terence, Dusetti, Nelson, Carrier, Alice, Ma, Stephanie, Ma, Man, Yuan, Xin-Yuan, Ma, Nelson, Ma, Alice |
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| Přispěvatelé: | City University of Hong Kong [Hong Kong] (CUHK), State key Laboratory for Liver Research, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University [Hong Kong] (POLYU), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sun Yat-sen University Cancer Center (SYSUCC) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Oncology MESH: Signal Transduction Cancer Research Lung Neoplasms [SDV]Life Sciences [q-bio] MESH: Heat-Shock Proteins Metastasis Mice 0302 clinical medicine MESH: Liver Neoplasms Tumor Cells Cultured MESH: Animals Neoplasm Metastasis MESH: Carcinoma Hepatocellular MESH: Mitogen-Activated Protein Kinase Phosphatases Heat-Shock Proteins Mitogen-Activated Protein Kinase 1 Mice Inbred BALB C Mitogen-Activated Protein Kinase 3 MESH: Protein Array Analysis Liver Neoplasms Prognosis 3. Good health 030220 oncology & carcinogenesis Hepatocellular carcinoma MESH: Dual-Specificity Phosphatases Dual-Specificity Phosphatases MESH: Tumor Protein p73 Signal transduction MESH: Mitogen-Activated Protein Kinase 3 Signal Transduction MESH: Mitogen-Activated Protein Kinase 1 medicine.medical_specialty MESH: Xenograft Model Antitumor Assays Carcinoma Hepatocellular Protein Array Analysis MESH: Mice Inbred BALB C Mice Nude MESH: Carrier Proteins [SDV.CAN]Life Sciences [q-bio]/Cancer Biology MESH: Prognosis 03 medical and health sciences MESH: Gene Expression Profiling Downregulation and upregulation Internal medicine Carcinoma medicine MESH: Mice Nude Animals Humans MESH: Tumor Cells Cultured neoplasms MESH: Mice MESH: Humans Gene Expression Profiling Cancer Tumor Protein p73 medicine.disease Xenograft Model Antitumor Assays MESH: Neoplasm Metastasis digestive system diseases MESH: Lung Neoplasms Gene expression profiling 030104 developmental biology Cancer research Mitogen-Activated Protein Kinase Phosphatases Carrier Proteins |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2017, 77 (17), pp.4602-4612. ⟨10.1158/0008-5472.CAN-16-3456⟩ Cancer Research, 2017, 77 (17), pp.4602-4612. ⟨10.1158/0008-5472.CAN-16-3456⟩ |
| ISSN: | 0008-5472 1538-7445 |
| Popis: | Identifying critical factors involved in the metastatic progression of hepatocellular carcinoma (HCC) may offer important therapeutic opportunities. Here, we report that the proapoptotic stress response factor TP53INP1 is often selectively downregulated in advanced stage IV and metastatic human HCC tumors. Mechanistic investigations revealed that TP53INP1 downregulation in early-stage HCC cells promoted metastasis via DUSP10 phosphatase-mediated activation of the ERK pathway. The DUSP10 promoter included putative binding sites for p73 directly implicated in modulation by TP53INP1. Overall, our findings show how TP53INP1 plays a critical role in limiting the progression of early-stage HCC, with implications for developing new therapeutic strategies to attack metastatic HCC. Cancer Res; 77(17); 4602–12. ©2017 AACR. |
| Databáze: | OpenAIRE |
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