ArticlePloS one2012
Side population in human non-muscle invasive bladder cancer enriches for cancer stem cells that are maintained by MAPK signalling.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- ABCG2-autophagy regulatory axis in cancer stem cells: implication in cancer metastasis, recurrence and chemotherapy resistance.Cell communication and signaling : CCS · 2026Review
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- Homeobox Gene Expression Dysregulation as Potential Diagnostic and Prognostic Biomarkers in Bladder Cancer.Diagnostics (Basel, Switzerland) · 2023Review
- FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer.Communications biology · 2023Article
- Sulforaphane and bladder cancer: a potential novel antitumor compound.Frontiers in pharmacology · 2023Review
- Pluripotency Stemness and Cancer: More Questions than Answers.Advances in experimental medicine and biology · 2022Article
- Impact of SOX2 function and regulation on therapy resistance in bladder cancer.Frontiers in oncology · 2022Review
- Multidrug efflux transporter ABCG2: expression and regulation.Cellular and molecular life sciences : CMLS · 2021Review
- Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.Cancers · 2021Article
- Non-Muscular Invasive Bladder Cancer: Re-envisioning Therapeutic Journey from Traditional to Regenerative Interventions.Aging and disease · 2021Review
- Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex.Cell death & disease · 2021Article
- Therapeutic and prognostic implications of NOTCH and MAPK signaling in bladder cancer.Cancer science · 2021Article
- The induction of core pluripotency master regulators in cancers defines poor clinical outcomes and treatment resistance.Oncogene · 2019Article
- Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy.Journal of medicinal chemistry · 2019Article
- Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target.Molecular cancer therapeutics · 2019Article
- Stem-Like Signature Predicting Disease Progression in Early Stage Bladder Cancer. The Role of E2F3 and SOX4.Biomedicines · 2018Review
- The dark side of SOX2: cancer - a comprehensive overview.Oncotarget · 2017Review
- RASAL2, a RAS GTPase-activating protein, inhibits stemness and epithelial-mesenchymal transition via MAPK/SOX2 pathway in bladder cancer.Cell death & disease · 2017Article
- Silencing expression of the NANOG gene and changes in migration and metastasis of urinary bladder cancer cells.Archives of medical science : AMS · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Side population (SP) and ABC transporter expression enrich for stem cells in numerous tissues. We explored if this phenotype characterised human bladder cancer stem cells (CSCs) and attempted to identify regulatory mechanisms. Focusing on non-muscle invasive bladder cancer (NMIBC), multiple human cell lines were used to characterise SP and ABC transporter expression. In vitro and in vivo phenotypic and functional assessments of CSC behaviour were undertaken. Expression of putative CSC marker ABCG2 was assessed in clinical NMIBC samples (n = 148), and a role for MAPK signalling, a central mechanism of bladder tumourigenesis, was investigated. Results showed that the ABCG2 transporter was predominantly expressed and was up-regulated in the SP fraction by 3-fold (ABCG2(hi)) relative to the non-SP (NSP) fraction (ABCG2(low)). ABCG2(hi) SP cells displayed enrichment of stem cell markers (Nanog, Notch1 and SOX2) and a three-fold increase in colony forming efficiency (CFE) in comparison to ABCG2(low) NSP cells. In vivo, ABCG2(hi) SP cells enriched for tumour growth compared with ABCG2(low) NSP cells, consistent with CSCs. pERK was constitutively active in ABCG2(hi) SP cells and MEK inhibition also inhibited the ABCG2(hi) SP phenotype and significantly suppressed CFE. Furthermore, on examining clinical NMIBC samples, ABCG2 expression correlated with increased recurrence and decreased progression free survival. Additionally, pERK expression also correlated with decreased progression free survival, whilst a positive correlation was further demonstrated between ABCG2 and pERK expression. In conclusion, we confirm ABCG2(hi) SP enriches for CSCs in human NMIBC and MAPK/ERK pathway is a suitable therapeutic target.
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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.