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AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer.
- Source :
- Cancers; Jun2019, Vol. 11 Issue 6, p785, 1p
- Publication Year :
- 2019
-
Abstract
- Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs. [ABSTRACT FROM AUTHOR]
- Subjects :
- ANIMAL experimentation
CANCER relapse
CELL culture
CELLULAR signal transduction
DRUG resistance in cancer cells
CLINICAL drug trials
GENE expression
IMMUNOHISTOCHEMISTRY
LONGITUDINAL method
GENETIC mutation
ONCOGENES
PHOSPHORYLATION
RATS
SARCOMA
SODIUM
SURVIVAL
THYROID gland tumors
TUMOR markers
DNA-binding proteins
PAPILLARY carcinoma
PROTEIN-tyrosine kinase inhibitors
THYMOMA
IN vitro studies
IODINE radioisotopes
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 137456419
- Full Text :
- https://doi.org/10.3390/cancers11060785