The Spemann organizer gene, Goosecoid , promotes tumor metastasis

Abstract

The process of invasion and metastasis during tumor progression is often reminiscent of cell migration events occurring during embryonic development. We hypothesized that genes controlling cellular changes in the Spemann organizer at gastrulation might be reactivated in tumors. The Goosecoid homeobox transcription factor is a known executer of cell migration from the Spemann organizer. We found that indeed Goosecoid is overexpressed in a majority of human breast tumors. Ectopic expression of Goosecoid in human breast cells generated invasion-associated cellular changes, including an epithelial-mesenchymal transition. TGF-␤ signaling, known to promote metastasis, induced Goosecoid expression in human breast cells. Moreover, Goosecoid significantly enhanced the ability of breast cancer cells to form pulmonary metastases in mice. These results demonstrate that Goosecoid promotes tumor cell malignancy and suggest that other conserved organizer genes may function similarly in human cancer. epithelial-mesenchymal transition

Control of gastrula cell motility by the Goosecoid/Mix.1/ Siamois network: Basic patterns and paradoxical effects

“…Cell motility is also important in tumor metastasis, and paradoxical effects should be of practical relevance here. A role for Gsc in tumor cell migration and metastasis has recently been described (Hartwell et al, 2006).…”

The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells

“…To date, several studies have revealed that many genes, such as oncogenes and tumor-suppressor genes, could be involved in complex metastatic processes, including tumor cell proliferation. For example, a few transcription factors that program many biological cell changes are required for executing the initial steps of the tumor invasion-metastasis cascade [28][29][30][31][32][33] . Med19 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II [9] .…”

The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells

“…HoxD10 impairs breast tumor cells migration (Carrio et al, 2005). Inversely, HoxD3 increases cell mobility and wound repair, while HoxB13 and Goosecoid promote invasion (Hansen et al, 2003;Zhao et al, 2005;Hartwell et al, 2006;Ohta et al, 2006). The cell spreading effect of HoxD3 correlates with its role in regulating cell-cell and cell-matrix interactions via the stimulation of integrin-a V b3 and reduction of Ecadherin (Hamada et al, 2001;Ohta et al, 2006).…”