Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer

Elvira Avilla, Valentina Guarino, Carla Visciano, Federica Liotti, Maria Svelto, GnanaPrakasam Krishnamoorthy, Renato Franco, Rosa Marina Melillo

Research output: Contribution to journalArticle

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Abstract

Thyroid cancer is the most common endocrine cancer, but its key oncogenic drivers remain undefined. In this study we identified the TYRO3 and AXL receptor tyrosine kinases as transcriptional targets of the chemokine CXCL12/SDF-1 in CXCR4-expressing thyroid cancer cells. Both receptors were constitutively expressed in thyroid cancer cell lines but not normal thyroid cells. AXL displayed high levels of tyrosine phosphorylation in most cancer cell lines due to constitutive expression of its ligand GAS6. In human thyroid carcinoma specimens, but not in normal thyroid tissues, AXL and GAS6 were often coexpressed. In cell lines expressing both receptors and ligand, blocking each receptor or ligand dramatically affected cell viability and decreased resistance to apoptotic stimuli. Stimulation of GAS6-negative cancer cells with GAS6 increased their proliferation and survival. Similarly, siRNA-mediated silencing of AXL inhibited cancer cell viability, invasiveness, and growth of tumor xenografts in nude mice. Our findings suggest that a TYRO3/AXL-GAS6 autocrine circuit sustains the malignant features of thyroid cancer cells and that targeting the circuit could offer a novel therapeutic approach in this cancer.

Original languageEnglish
Pages (from-to)1792-1804
Number of pages13
JournalCancer Research
Volume71
Issue number5
DOIs
Publication statusPublished - Mar 1 2011

Fingerprint

Receptor Protein-Tyrosine Kinases
Thyroid Neoplasms
Neoplasms
Ligands
Cell Line
Cell Survival
Thyroid Gland
Endocrine Gland Neoplasms
Chemokine CXCL12
Heterografts
Nude Mice
Small Interfering RNA
Tyrosine
Phosphorylation
Survival
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Avilla, E., Guarino, V., Visciano, C., Liotti, F., Svelto, M., Krishnamoorthy, G., ... Melillo, R. M. (2011). Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer. Cancer Research, 71(5), 1792-1804. https://doi.org/10.1158/0008-5472.CAN-10-2186

Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer. / Avilla, Elvira; Guarino, Valentina; Visciano, Carla; Liotti, Federica; Svelto, Maria; Krishnamoorthy, GnanaPrakasam; Franco, Renato; Melillo, Rosa Marina.

In: Cancer Research, Vol. 71, No. 5, 01.03.2011, p. 1792-1804.

Research output: Contribution to journalArticle

Avilla, E, Guarino, V, Visciano, C, Liotti, F, Svelto, M, Krishnamoorthy, G, Franco, R & Melillo, RM 2011, 'Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer', Cancer Research, vol. 71, no. 5, pp. 1792-1804. https://doi.org/10.1158/0008-5472.CAN-10-2186
Avilla E, Guarino V, Visciano C, Liotti F, Svelto M, Krishnamoorthy G et al. Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer. Cancer Research. 2011 Mar 1;71(5):1792-1804. https://doi.org/10.1158/0008-5472.CAN-10-2186
Avilla, Elvira ; Guarino, Valentina ; Visciano, Carla ; Liotti, Federica ; Svelto, Maria ; Krishnamoorthy, GnanaPrakasam ; Franco, Renato ; Melillo, Rosa Marina. / Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer. In: Cancer Research. 2011 ; Vol. 71, No. 5. pp. 1792-1804.
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