ArticleMolecular oncology2020
Distinct roles of PIK3CA in the enrichment and maintenance of cancer stem cells in head and neck squamous cell carcinoma.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Vertical inhibition of p110α/AKT and N-cadherin enhances treatment efficacy in PIK3CA-aberrated ovarian cancer cells.Molecular oncology · 2025Article
- MiR-592 Attenuates Tamoxifen Resistance in Breast Cancer Through PIK3CA-Mediated PI3K/AKT/mTOR Signaling Pathway.Applied biochemistry and biotechnology · 2025Article
- Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges.Biomedicines · 2024Review
- CombinedInternational journal of molecular sciences · 2024Article
- Exploring the mechanism of Cassiae semen in regulating lipid metabolism through network pharmacology and experimental validation.Bioscience reports · 2023Article
- Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.American journal of cancer research · 2023Review
- Epidermal growth factor receptor signaling in precancerous keratinocytes promotes neighboring head and neck cancer squamous cell carcinoma cancer stem cell-like properties and phosphoinositide 3-kinase inhibitor insensitivity.Molecular carcinogenesis · 2022Article
- Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma.Molecular cancer · 2022Article
- Article
- Therapeutic implications of activating noncanonical PIK3CA mutations in head and neck squamous cell carcinoma.The Journal of clinical investigation · 2021Article
- Systemic immune responses are associated with molecular characteristics of circulating tumor cells in head and neck squamous cell carcinoma.Molecular and clinical oncology · 2021Article
- A novel diphtheria toxin-based bivalent human EGF fusion toxin for treatment of head and neck squamous cell carcinoma.Molecular oncology · 2021Article
- CSMD1 Mutation Related to Immunity Can Be Used as a Marker to Evaluate the Clinical Therapeutic Effect and Prognosis of Patients with Esophageal Cancer.International journal of general medicine · 2021Article
- PI3K in stemness regulation: from development to cancer.Biochemical Society transactions · 2020Review
- NTRK Fusions and TRK Inhibitors: Potential Targeted Therapies for Adult Glioblastoma.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Recurrence and metastasis are the major causes of mortality in head and neck squamous cell carcinoma (HNSCC). It is suggested that cancer stem cells (CSCs) play pivotal roles in recurrence and metastasis. Thus, a greater understanding of the mechanisms of CSC regulation may provide opportunities to develop novel therapies for improving survival by controlling recurrence or metastasis. Here, we report that overexpression of the gene encoding the catalytic subunit of PI3K (PIK3CA), the most frequently amplified oncogene in HNSCC, promotes epithelial-to-mesenchymal transition and enriches the CSC population. However, PIK3CA is not required to maintain these traits and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway paradoxically promotes CSC population. Molecular analysis revealed that overexpression of PIK3CA activates multiple receptor tyrosine kinases (RTKs), in which ephrin receptors (Ephs), tropomyosin receptor kinases (TRK) and mast/stem cell growth factor receptor (c-Kit) contribute to maintain CSC population. Accordingly, simultaneous inhibition of these RTKs using a multi-kinase inhibitor ponatinib has a superior effect at eliminating the CSC population and reduces metastasis of PIK3CA-overexpressing HNSCC cells. Our result suggests that co-targeting of Ephs, TRKs and the c-Kit pathway may be effective at eliminating the PI3K-independent CSC population, thereby providing potential targets for future development of a novel anti-CSC therapeutic approach for HNSCC patients, particularly for patients with PIK3CA amplification.
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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.