施佩曼组织者基因“原肠胚形成蛋白”促进肿瘤转移。
The Spemann organizer gene, Goosecoid, promotes tumor metastasis.
作者信息
Hartwell Kimberly A, Muir Beth, Reinhardt Ferenc, Carpenter Anne E, Sgroi Dennis C, Weinberg Robert A
机构信息
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
出版信息
Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18969-74. doi: 10.1073/pnas.0608636103. Epub 2006 Dec 1.
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.
肿瘤进展过程中的侵袭和转移过程常常让人联想到胚胎发育过程中发生的细胞迁移事件。我们推测，在原肠胚形成期控制斯佩曼组织者中细胞变化的基因可能在肿瘤中重新激活。鹅膏蕈氨酸同源框转录因子是已知的从斯佩曼组织者进行细胞迁移的执行者。我们发现，事实上鹅膏蕈氨酸在大多数人类乳腺肿瘤中过度表达。在人乳腺细胞中异位表达鹅膏蕈氨酸会产生与侵袭相关的细胞变化，包括上皮-间质转化。已知促进转移的转化生长因子-β信号传导在人乳腺细胞中诱导鹅膏蕈氨酸表达。此外，鹅膏蕈氨酸显著增强了乳腺癌细胞在小鼠体内形成肺转移的能力。这些结果表明，鹅膏蕈氨酸促进肿瘤细胞恶性化，并提示其他保守的组织者基因可能在人类癌症中发挥类似作用。
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