TY - JOUR
T1 - Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor
AU - Davis, Paul J.
AU - Davis, Faith B.
AU - Lin, Hung Yun
AU - Mousa, Shaker A.
AU - Zhou, Min
AU - Luidens, Mary K.
PY - 2009/12
Y1 - 2009/12
N2 - A thyroid hormone receptor on integrin αvβ3 that mediates cell surface-initiated nongenomic actions of thyroid hormone on tumor cell proliferation and on angiogenesis has been described. Transduction of the hormone signal into these recently recognized proliferative effects is by extracellular-regulated kinases 1/2 (ERK1/2). Other nongenomic actions of the hormone may be transduced by phosphatidylinositol 3-kinase (PI3K) and are initiated in cytoplasm or at the cell surface. PI3K-mediated effects are important to angiogenesis or other recently appreciated cell functions but apparently not to tumor cell division. For those actions of thyroid hormone [L-thyroxine (T4) and 3,3′-5-triiodo-L-thyronine (T 3)] that begin at the integrin receptor, tetraiodothyroacetic acid (tetrac) is an inhibitor of and probe for the participation of the receptor in downstream intracellular events. In addition, tetrac has actions initiated at the integrin receptor that are unrelated to inhibition of the effects of T 4 and T3 but do involve gene transcription in tumor cells. Discussed here are the implications of translating these nongenomic mechanisms of thyroid hormone analogs into clinical cancer cell biology, tumor-related angiogenesis, and modulation of angiogenesis that is not related to cancer.
AB - A thyroid hormone receptor on integrin αvβ3 that mediates cell surface-initiated nongenomic actions of thyroid hormone on tumor cell proliferation and on angiogenesis has been described. Transduction of the hormone signal into these recently recognized proliferative effects is by extracellular-regulated kinases 1/2 (ERK1/2). Other nongenomic actions of the hormone may be transduced by phosphatidylinositol 3-kinase (PI3K) and are initiated in cytoplasm or at the cell surface. PI3K-mediated effects are important to angiogenesis or other recently appreciated cell functions but apparently not to tumor cell division. For those actions of thyroid hormone [L-thyroxine (T4) and 3,3′-5-triiodo-L-thyronine (T 3)] that begin at the integrin receptor, tetraiodothyroacetic acid (tetrac) is an inhibitor of and probe for the participation of the receptor in downstream intracellular events. In addition, tetrac has actions initiated at the integrin receptor that are unrelated to inhibition of the effects of T 4 and T3 but do involve gene transcription in tumor cells. Discussed here are the implications of translating these nongenomic mechanisms of thyroid hormone analogs into clinical cancer cell biology, tumor-related angiogenesis, and modulation of angiogenesis that is not related to cancer.
UR - http://www.scopus.com/inward/record.url?scp=72249119235&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72249119235&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00480.2009
DO - 10.1152/ajpendo.00480.2009
M3 - Review article
C2 - 19755667
AN - SCOPUS:72249119235
SN - 0193-1849
VL - 297
SP - E1238-E1246
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 6
ER -