Journal
CANCERS
Volume 11, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/cancers11060785
Keywords
AXL; radioactive iodine (RAI)-refractoriness; disease persistence/recurrence; p65 NF-kB activation; thyroid cancer
Categories
Funding
- Italian Ministry of Health
- Associazione Italiana per la Ricerca sul Cancro (AIRC) IG grant [16829]
- POR CAMPANIA FESR 2014/2020-Manifestazione di interesse per la realizzazione di Technology Platform nell'ambito della lotta alle patologie oncologiche - RARE.PLAT.NET and SATIN
- Istituto Superiore di Oncologia grant [MIUR PON01_02782/12]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available