The Spemann organizer gene, Goosecoid, promotes tumor metastasis.
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-beta 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.
Hartwell
Kimberly A
KA
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Muir
Beth
B
Reinhardt
Ferenc
F
Carpenter
Anne E
AE
Sgroi
Dennis C
DC
Weinberg
Robert A
RA
D000375:Aging / Q000502:physiology; D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051956:Goosecoid Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology*; D020897:Organizers, Embryonic / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D014408:Biomarkers, Tumor; D051956:Goosecoid Protein; D016212:Transforming Growth Factor beta