Integrin alphaVbeta3 acting as membrane receptor for thyroid hormones medi

CAYROL F; DÍAZ FLAQUÉ MC; FERNANDO T; YANG SN; STERLE HA; BOLONTRADE M; AMORÓS M; ISSE B; FARÍAS RN; AHN H; TIAN YF; TABBO F; SINGH A; INGHIRAMI G; CERCHIETTI L; CREMASCHI GA

BLOOD, THE JOURNAL OF THE AMERICAN SOCIETY OF HEMATOLOGY - PRINT

AMER SOC HEMATOLOGY

Lugar: Washington, DC; Año: 2015 vol. 25 p. 841 - 851

0006-4971

The interaction of lymphoid tumor cells with components of the extracellular matrix via the integrin αvβ3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones in several tissues. We found that thyroid hormones (THs), acting as soluble integrin αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCL). Specifically, TH-activated αvβ3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the up-regulation of VEGF. Consequently, genetic or pharmacologic inhibition of integrin αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenografts models. In sum, we here show that integrin αVβ3 transduces pro-survival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment for TCL patients.