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Homeodomain-interacting protein kinase 2 suppresses proliferation and aerobic glycolysis via ERK/cMyc axis in pancreatic cancer.
Cell Prolif 2019; 52(3):e12603CP

Abstract

OBJECTIVES

To investigate the roles of the homeodomain-interacting protein kinase (HIPK) family of proteins in pancreatic cancer prognosis and the possible molecular mechanism.

MATERIALS AND METHODS

The expression of HIPK family genes and their roles in pancreatic cancer prognosis were analysed by using The Cancer Genome Atlas (TCGA). The roles of HIPK2 in pancreatic cancer proliferation and glycolysis were tested by overexpression of HIPK2 in pancreatic cancer cells, followed by cell proliferation assay, glucose uptake analysis and Seahorse extracellular flux analysis. The mechanism of action of HIPK2 in pancreatic cancer proliferation and glycolysis was explored by examining its effect on the ERK/cMyc axis.

RESULTS

Decreased HIPK2 expression indicated worse prognosis of pancreatic cancer. Overexpression of HIPK2 in pancreatic cancer cells decreased cell proliferation and attenuated aerobic glycolysis, which sustained proliferation of cancer cells. HIPK2 decreased cMyc protein levels and expression of cMyc-targeted glycolytic genes. cMyc was a mediator that regulated HIPK2-induced decrease in aerobic glycolysis. HIPK2 regulated cMyc protein stability via ERK activation, which phosphorylated and controlled cMyc protein stability.

CONCLUSIONS

HIPK2 suppressed proliferation of pancreatic cancer in part through inhibiting the ERK/cMyc axis and related aerobic glycolysis.

Authors+Show Affiliations

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Pancreatic Cancer Institute, Shanghai, China. Pancreatic Cancer Institute, Fudan University, Shanghai, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30932257

Citation

Qin, Yi, et al. "Homeodomain-interacting Protein Kinase 2 Suppresses Proliferation and Aerobic Glycolysis Via ERK/cMyc Axis in Pancreatic Cancer." Cell Proliferation, vol. 52, no. 3, 2019, pp. e12603.
Qin Y, Hu Q, Ji S, et al. Homeodomain-interacting protein kinase 2 suppresses proliferation and aerobic glycolysis via ERK/cMyc axis in pancreatic cancer. Cell Prolif. 2019;52(3):e12603.
Qin, Y., Hu, Q., Ji, S., Xu, J., Dai, W., Liu, W., ... Xu, X. (2019). Homeodomain-interacting protein kinase 2 suppresses proliferation and aerobic glycolysis via ERK/cMyc axis in pancreatic cancer. Cell Proliferation, 52(3), pp. e12603. doi:10.1111/cpr.12603.
Qin Y, et al. Homeodomain-interacting Protein Kinase 2 Suppresses Proliferation and Aerobic Glycolysis Via ERK/cMyc Axis in Pancreatic Cancer. Cell Prolif. 2019;52(3):e12603. PubMed PMID: 30932257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homeodomain-interacting protein kinase 2 suppresses proliferation and aerobic glycolysis via ERK/cMyc axis in pancreatic cancer. AU - Qin,Yi, AU - Hu,Qiangsheng, AU - Ji,Shunrong, AU - Xu,Jin, AU - Dai,Weixing, AU - Liu,Wensheng, AU - Xu,Wenyan, AU - Sun,Qiqing, AU - Zhang,Zheng, AU - Ni,Quanxing, AU - Yu,Xianjun, AU - Zhang,Bo, AU - Xu,Xiaowu, Y1 - 2019/04/01/ PY - 2018/09/26/received PY - 2019/02/16/revised PY - 2019/02/22/accepted PY - 2019/4/2/pubmed PY - 2019/6/18/medline PY - 2019/4/2/entrez KW - ERK KW - HIPK2 KW - cMyc KW - glycolysis KW - pancreatic cancer KW - proliferation SP - e12603 EP - e12603 JF - Cell proliferation JO - Cell Prolif. VL - 52 IS - 3 N2 - OBJECTIVES: To investigate the roles of the homeodomain-interacting protein kinase (HIPK) family of proteins in pancreatic cancer prognosis and the possible molecular mechanism. MATERIALS AND METHODS: The expression of HIPK family genes and their roles in pancreatic cancer prognosis were analysed by using The Cancer Genome Atlas (TCGA). The roles of HIPK2 in pancreatic cancer proliferation and glycolysis were tested by overexpression of HIPK2 in pancreatic cancer cells, followed by cell proliferation assay, glucose uptake analysis and Seahorse extracellular flux analysis. The mechanism of action of HIPK2 in pancreatic cancer proliferation and glycolysis was explored by examining its effect on the ERK/cMyc axis. RESULTS: Decreased HIPK2 expression indicated worse prognosis of pancreatic cancer. Overexpression of HIPK2 in pancreatic cancer cells decreased cell proliferation and attenuated aerobic glycolysis, which sustained proliferation of cancer cells. HIPK2 decreased cMyc protein levels and expression of cMyc-targeted glycolytic genes. cMyc was a mediator that regulated HIPK2-induced decrease in aerobic glycolysis. HIPK2 regulated cMyc protein stability via ERK activation, which phosphorylated and controlled cMyc protein stability. CONCLUSIONS: HIPK2 suppressed proliferation of pancreatic cancer in part through inhibiting the ERK/cMyc axis and related aerobic glycolysis. SN - 1365-2184 UR - https://www.unboundmedicine.com/medline/citation/30932257/Homeodomain-interacting_protein_kinase_2_suppresses_proliferation_and_aerobic_glycolysis_via_ERK/cMyc_axis_in_pancreatic_cancer L2 - https://doi.org/10.1111/cpr.12603 DB - PRIME DP - Unbound Medicine ER -