2026-08-10T08:12:00Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/272452026-02-21T01:17:32Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991
Repisalud
author
MartÃnez-Iglesias, Olaia
author
Garcia-Silva, Susana
author
Tenbaum, Stephan P
author
Regadera, Javier
author
Larcher, Fernando
author
Paramio, Jesus M
author
Vennström, Bjorn
author
Aranda, Ana
2026-02-20T21:06:44Z
2026-02-20T21:06:44Z
2009-01-15
Cancer Res . 2009 Jan 15;69(2):501-9.
Cancer Research
19147563
https://hdl.handle.net/20.500.12105/27245
Loss of thyroid hormone receptors (TR) is a common feature in some tumors, although their role in tumor progression is currently unknown. We show here that expression of TRbeta1 in hepatocarcinoma and breast cancer cells reduces tumor growth, causes partial mesenchymal-to-epithelial cell transition, and has a striking inhibitory effect on invasiveness, extravasation, and metastasis formation in mice. In cultured cells, TRbeta1 abolishes anchorage-independent growth and migration, blocks responses to epidermal growth factor, insulin-like growth factor-I, and transforming growth factor beta, and regulates expression of genes that play a key role in tumorigenicity and metastatic growth. The receptor disrupts the mitogenic action of growth factors by suppressing activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling pathways that are crucial for cell proliferation and invasiveness. Furthermore, increased aggressiveness of skin tumors is found in genetically modified mice lacking TRs, further demonstrating the role of these receptors as inhibitors of tumor progression. These results define a novel role for the thyroid hormone receptor as a metastasis suppressor gene, providing a starting point for the development of novel therapeutic strategies for the treatment of human cancer.
eng
CARCINOMA
RAS
MICE
MUTATION
CHEMOKINE
PROGNOSTIC-FACTOR
C-MET
GENE-EXPRESSION
HEPATOCYTE GROWTH FACTOR
BREAST CANCER METASTASIS
Thyroid hormone receptor beta1 acts as a potent suppressor of tumor invasiveness and metastasis.
research article
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