ArticleOncogene2013
WIP1 phosphatase modulates the Hedgehog signaling by enhancing GLI1 function.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Genomics of Primary and Metastatic Cutaneous Melanoma: A Systematic Review and Meta-Analysis.American journal of clinical dermatology · 2026Pooled it
- The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Pooled it
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- Cancer Stem Cell Regulation as a Target of Therapeutic Intervention: Insights into Breast, Cervical and Lung Cancer.Cell biochemistry and biophysics · 2025Review
- The MEK5/ERK5 pathway promotes the activation of the Hedgehog/GLI signaling in melanoma cells.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines.International journal of oncology · 2024Article
- Inhibition of GLI Transcriptional Activity and Prostate Cancer Cell Growth and Proliferation by DAX1.Current issues in molecular biology · 2023Article
- Inhibition of ERK5 Elicits Cellular Senescence in Melanoma via the Cyclin-Dependent Kinase Inhibitor p21.Cancer research · 2022Article
- The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells.International journal of molecular sciences · 2021Article
- Inactivating p53 is essential for nerve growth factor receptor to promote melanoma-initiating cell-stemmed tumorigenesis.Cell death & disease · 2020Article
- Phosphoproteomics of short-term hedgehog signaling in human medulloblastoma cells.Cell communication and signaling : CCS · 2020Article
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- Review
- Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened.Frontiers in genetics · 2019Review
- Review
- Role of GLI Transcription Factors in Pathogenesis and Their Potential as New Therapeutic Targets.International journal of molecular sciences · 2018Review
- Targeted inhibition of Hedgehog-GLI signaling by novel acylguanidine derivatives inhibits melanoma cell growth by inducing replication stress and mitotic catastrophe.Cell death & disease · 2018Article
- The emerging roles of phosphatases in Hedgehog pathway.Cell communication and signaling : CCS · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hedgehog-GLI (HH-GLI) signaling plays a critical role in controlling growth and tissue patterning during embryogenesis and is implicated in a variety of human malignancies, including those of the skin. Phosphorylation events have been shown to regulate the activity of the GLI transcription factors, the final effectors of the HH-GLI signaling pathway. Here, we show that WIP1 (or PPM1D), an oncogenic phosphatase amplified/overexpressed in several types of human cancer, is a positive modulator of the HH signaling. Mechanistically, WIP1 enhances the function of GLI1 by increasing its transcriptional activity, nuclear localization and protein stability, but not of GLI2 nor GLI3. We also find that WIP1 and GLI1 are in a complex. Modulation of the transcriptional activity of GLI1 by WIP1 depends on the latter's phosphatase activity and, remarkably, does not require p53, a known WIP1 target. Functionally, we find that WIP1 is required for melanoma and breast cancer cell proliferation and self-renewal in vitro and melanoma xenograft growth induced by activation of the HH signaling. Pharmacological blockade of the HH pathway with the SMOOTHENED antagonist cyclopamine acts synergistically with inhibition of WIP1 in reducing growth of melanoma and breast cancer cells in vitro. Overall, our data uncover a role for WIP1 in modulating the activity of GLI1 and in sustaining cancer cell growth and cancer stem cell self-renewal induced by activation of the HH pathway. These findings open a novel therapeutic approach for human melanomas and, possibly, other cancer types expressing WIP1 and with activated HH pathway.
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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.