ArticleOncotarget2014
Inhibition of STAT3 signaling targets both tumor-initiating and differentiated cell populations in prostate cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 62 citations in OpenAlex.
- Biobank of genetically defined murine prostate cancer tumoroids uncovers oncogenic pathways and drug vulnerabilities driven by PTEN-loss.Cell reports methods · 2026Article
- Review
- Improvement of Docetaxel Efficacy through Simultaneous Blockade of Transcription Factors NF-κB and STAT-3 Using Pentoxifylline and Stattic in Prostate Cancer Cells.Current issues in molecular biology · 2024Article
- Review
- Understanding and targeting prostate cancer cell heterogeneity and plasticity.Seminars in cancer biology · 2022Review
- LIN28B Enhanced STAT3 Signaling Regulates Inflammatory Response and Chemotherapeutic Resistance in Cholangiocytes.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Impact of STAT Proteins in Tumor Progress and Therapy Resistance in Advanced and Metastasized Prostate Cancer.Cancers · 2021Review
- Review
- Binge-like ethanol drinking activates anaplastic lymphoma kinase signaling and increases the expression of STAT3 target genes in the mouse hippocampus and prefrontal cortex.Genes, brain, and behavior · 2021Article
- STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population.Scientific reports · 2020Article
- Antiangiogenesis Efficacy of Ethanol Extract fromEvidence-based complementary and alternative medicine : eCAM · 2020Article
- Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications.Medicines (Basel, Switzerland) · 2019Review
- Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells.Frontiers in oncology · 2019Review
- IL-6 mediates platinum-induced enrichment of ovarian cancer stem cells.JCI insight · 2018Article
- The natural polyphenol curcumin induces apoptosis by suppressing STAT3 signaling in esophageal squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2018Article
- Spider peptide toxin lycosin-I induces apoptosis and inhibits migration of prostate cancer cells.Experimental biology and medicine (Maywood, N.J.) · 2018Article
- Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome.Oncotarget · 2018Article
- Jazf1 promotes prostate cancer progression by activating JNK/Slug.Oncotarget · 2018Article
- GMI ablates cancer stemness and cisplatin resistance in oral carcinomas stem cells through IL-6/Stat3 signaling inhibition.Oncotarget · 2017Article
- Interleukin-6 identified as an important factor in hypoxia- and aldehyde dehydrogenase-based gefitinib adaptive resistance in non-small cell lung cancer cells.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite of tremendous research efforts to profile prostate cancer, the genetic alterations and biological processes that correlate with disease progression remain partially elusive. In this study we show that the STAT3 small molecule inhibitor Stattic caused S-phase accumulation at low-dose levels and led to massive apoptosis at a relatively high-dose level in prostate cancer cells. STAT3 knockdown led to the disruption of the microvascular niche which tumor-initiating cells (TICs) and non-tumor initiating cells (non-TICs)depend on. Primary human prostate cancer cells and prostate cancer cell line contained high aldehyde dehydrogenase activity (ALDH(high)) subpopulations with stem cell-like characteristics, which expressed higher levels of the active phosphorylated form of STAT3 (pSTAT3) than that of non-ALDH(high) subpopulations. Stattic could singnificantly decrease the population of ALDH(high) prostate cancer cells even at low-dose levels. IL-6 can convert non-ALDH(high) cells to ALDH(high) cells in prostate cancer cell line as well as from cells derived from human prostate tumors, the conversion mediated by IL-6 was abrogated in the presence of STAT3 inhibitor or upon STAT3 knockdown. STAT3 knockdown significantly impaired the ability of prostate cancer cells to initiate development of prostate adenocarcinoma. Moreover, blockade of STAT3 signaling was significantly effective in eradicating the tumor-initiating and bulk tumor cancer cell populations in both prostate cancer cell-line xenograft model and patient-derived tumor xenograft (PDTX) models. This data suggests that targeting both tumor initiating and differentiated cell populations by STAT3 inhibition is predicted to have greater efficacy for prostate cancer treatment.
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