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
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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