ArticleCancer research2009
Proteasome-mediated degradation and functions of hematopoietic progenitor kinase 1 in pancreatic cancer.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Glioblastoma cellular MAP4K1 facilitates tumor growth and disrupts T effector cell infiltration.Life science alliance · 2023Article
- Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia.The Journal of clinical investigation · 2023Article
- Decreased Jumonji Domain-Containing 3 at the Promoter Downregulates Hematopoietic Progenitor Kinase 1 Expression and Cytoactivity of T Follicular Helper Cells from Systemic Lupus Erythematosus Patients.Journal of immunology research · 2022Article
- Review
- Hematopoietic progenitor kinase 1 down-regulates the oncogenic receptor tyrosine kinase AXL in pancreatic cancer.The Journal of biological chemistry · 2020Article
- Mitogen-Activated Protein Kinase Inhibitors and T-Cell-Dependent Immunotherapy in Cancer.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Investigation of Novel Regulation of N-myristoyltransferase by Mammalian Target of Rapamycin in Breast Cancer Cells.Scientific reports · 2018Article
- HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.Molecular medicine reports · 2017Article
- Suppression of pancreatic cancer growth and metastasis by HMP19 identified through genome-wide shRNA screen.International journal of cancer · 2016Article
- GLK/MAP4K3 overexpression associates with recurrence risk for non-small cell lung cancer.Oncotarget · 2016Article
- Article
- Pro-oncogenic function of HIP-55/Drebrin-like (DBNL) through Ser269/Thr291-phospho-sensor motifs.Oncotarget · 2014Article
- The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1.The Journal of biological chemistry · 2014Article
- Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2012Article
- Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of 1α,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML cells and as a mediator of vitamin D resistance.Cell cycle (Georgetown, Tex.) · 2012Article
- Aurora kinase A promotes ovarian tumorigenesis through dysregulation of the cell cycle and suppression of BRCA2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. In this study, we examined the expression, regulation, and functions of HPK1 in pancreatic ductal adenocarcinomas (PDA). We found that loss of HPK1 protein expression correlated significantly with the progression of pancreatic intraepithelial neoplasias (P = 0.001) and development of invasive PDA. Similarly, HPK1 protein was not expressed in any of eight PDA cell lines examined but was expressed in immortalized human pancreatic duct epithelial (HPDE) cells. There was no difference in HPK1 mRNA levels in PDA cell lines or primary PDA compared with those in HPDE cells or ductal epithelium in chronic pancreatitis and normal pancreas, respectively. Treatment of Panc-1 cells with a proteasome inhibitor, MG132, increased the HPK1 protein levels in a dose-dependent manner, suggesting that alteration in proteasome activity contributes to the loss of HPK1 protein expression in pancreatic cancer. Like the endogenous HPK1, both wild-type HPK1 and its kinase-dead mutant, HPK1-M46, overexpressed in Panc-1 cells, were also targeted by proteasome-mediated degradation. After MG132 withdrawal, wild-type HPK1 protein expression was markedly decreased within 24 hours, but kinase-dead HPK1 mutant protein expression was sustained for up to 96 hours. Therefore, HPK1 kinase activities were required for the loss of HPK1 protein in PDAs. Furthermore, restoring wild-type HPK1 protein in PDA cells led to the increase in p21 and p27 protein expression and cell cycle arrest. Thus, HPK1 may function as a novel tumor suppressor and its loss plays a critical role in pancreatic cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.