Hypoxic niches are endowed with a protumorigenic mechanism that supersedes the protective function of PTEN
Autor: | Cristiane H. Squarize, L. Webber, Carlos H. V. Nascimento-Filho, Eny Maria Goloni-Bertollo, Rogerio M. Castilho, Gabriell B. Borgato |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Mice Nude Apoptosis Malignancy Biochemistry Mice 03 medical and health sciences 0302 clinical medicine stomatognathic system Cell Movement Cancer stem cell Tumor Cells Cultured otorhinolaryngologic diseases Genetics medicine Animals Humans PTEN Neoplasm Invasiveness Epithelial–mesenchymal transition Hypoxia neoplasms Molecular Biology PI3K/AKT/mTOR pathway Cell Proliferation biology Squamous Cell Carcinoma of Head and Neck Mechanism (biology) Research PTEN Phosphohydrolase Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Xenograft Model Antitumor Assays Head and neck squamous-cell carcinoma Gene Expression Regulation Neoplastic stomatognathic diseases 030104 developmental biology Head and Neck Neoplasms Neoplastic Stem Cells biology.protein Cancer research Female 030217 neurology & neurosurgery Function (biology) Signal Transduction Biotechnology |
Zdroj: | FASEB J |
ISSN: | 1530-6860 0892-6638 |
Popis: | Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide and is characterized by a fast-paced growth. Like other solid tumors, the HNSCC growth rate results in the development of hypoxic regions identified by the expression of hypoxia-inducible factor 1α (HIF-1α). Interestingly, clinical data have shown that pharmacological induction of intratumoral hypoxia caused an unexpected rise in tumor metastasis and the accumulation of cancer stem cells (CSCs). However, little is known on the molecular circuitries involved in the presence of intratumoral hypoxia and the augmented population of CSCs. Here we explore the impact of hypoxia on the behavior of HNSCC and define that the controlling function of phosphatase and tensin homolog (PTEN) over HIF-1α expression and CSC accumulation are de-regulated during hypoxic events. Our findings indicate that hypoxic niches are poised to accumulate CSCs in a molecular process driven by the loss of PTEN activity. Furthermore, our data suggest that targeted therapies aiming at the PTEN/PI3K signaling may constitute an effective strategy to counteract the development of intratumoral hypoxia and the accumulation of CSCs.—Nascimento-Filho, C. H. V., Webber, L. P., Borgato, G. B., Goloni-Bertollo, E. M., Squarize, C. H., Castilho, R. M. Hypoxic niches are endowed with a protumorigenic mechanism that supersedes the protective function of PTEN. |
Databáze: | OpenAIRE |
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