ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer cells and enhances the therapeutic efficacy of BH3 mimetics.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- An Open-label, Phase II Trial of Entospletinib (GS-9973), a Selective Spleen Tyrosine Kinase Inhibitor, in Diffuse Large B-cell Lymphoma.Clinical lymphoma, myeloma & leukemia · 2018Trial
- Interconnection of CD133 Stem Cell Marker with Autophagy and Apoptosis in Colorectal Cancer.International journal of molecular sciences · 2024Review
- Coding, or non-coding, that is the question.Cell research · 2024Review
- A pan-cancer analysis of pituitary tumor-transforming 3, pseudogene.American journal of translational research · 2023Article
- Article
- A Restriction Endonuclease-Based Assay to Distinguish NANOGP8 Retrogene from Parental NANOG.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Overexpression of miR-382 Sensitizes Hepatocellular Carcinoma Cells to γδ T Cells by Inhibiting the Expression of c-FLIP.Molecular therapy oncolytics · 2020Article
- TIAM1 promotes chemoresistance and tumor invasiveness in colorectal cancer.Cell death & disease · 2019Article
- The Pseudogene PTTG3P Promotes Cell Migration and Invasion in Esophageal Squamous Cell Carcinoma.Open medicine (Warsaw, Poland) · 2019Article
- Prognostic significance of NANOG expression in solid tumors: a meta-analysis.OncoTargets and therapy · 2018Review
- Therapeutic strategies against cancer stem cells in human colorectal cancer.Oncology letters · 2017Article
- PTTG3P promotes gastric tumour cell proliferation and invasion and is an indicator of poor prognosis.Journal of cellular and molecular medicine · 2017Article
- HDAC1 Upregulation by NANOG Promotes Multidrug Resistance and a Stem-like Phenotype in Immune Edited Tumor Cells.Cancer research · 2017Article
- Pathways and mechanisms of venetoclax resistance.Leukemia & lymphoma · 2017Review
- Histone Deacetylase Inhibitor Enhances the Efficacy of MEK Inhibitor through NOXA-Mediated MCL1 Degradation in Triple-Negative and Inflammatory Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- MCL-1 Depletion Impairs DNA Double-Strand Break Repair and Reinitiation of Stalled DNA Replication Forks.Molecular and cellular biology · 2017Article
- Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo.Oncotarget · 2016Article
- Clinical implications of the coexpression of SRC1 and NANOG in HER-2-overexpressing breast cancers.OncoTargets and therapy · 2016Article
- Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment.Biochimica et biophysica acta · 2015Review
- Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeHigh levels of BCL-2 family members in colorectal carcinoma cause resistance to treatment. Inhibition of NANOG or its paralog NANOGP8 reduces the proliferation, stemness, and tumorigenicity of colorectal carcinoma cells. Our hypothesis was that inhibition of NANOG/NANOGP8 enhances the cytotoxic effect of BH3 mimetics targeting BCL-2 family members in colorectal carcinoma cells through reducing expression of MCL-1, a prosurvival BCL-2 protein. EXPERIMENTAL
designLentiviral vector (LV) shRNA to NANOG (shNG-1) or NANOGP8 (shNp8-1) transduced colorectal carcinoma cells that were also exposed to the BH3 mimetics ABT-737 or ABT-199 in vivo in colorectal carcinoma xenografts and in vitro where proliferation, protein and gene expression, and apoptosis were measured.
resultsClone A and CX-1 were sensitive to ABT-737 and ABT-199 at IC50s of 2 to 9 μmol/L but LS174T was resistant with IC50s of 18 to 30 μmol/L. Resistance was associated with high MCL-1 expression in LS174T. LVshNG-1 or LVshNp8-1 decreased MCL-1 expression, increased apoptosis, and decreased replating efficiency in colorectal carcinoma cells treated with either ABT-737 or ABT-199 compared with the effects of either BH3 mimetic alone. Inhibition or overexpression of MCL-1 alone replicated the effects of LVshNG-1 or LVshNp8-1 in increasing or decreasing the apoptosis caused with the BH3 mimetic. The combination therapy inhibited the growth of LS174T xenografts in vivo compared with untreated controls or treatment with only LV shRNA or ABT-737.
conclusionsInhibition of NANOGP8 or NANOG enhances the cytotoxicity of BH3 mimetics that target BCL-2 family members. Gene therapy targeting the NANOGs may increase the efficacy of BH3 mimetics in colorectal carcinoma.
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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.