Sherwood David R, Butler James A, Kramer James M, Sternberg Paul W
HHMI and Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.
Cell. 2005 Jun 17;121(6):951-62. doi: 10.1016/j.cell.2005.03.031.
Cell invasion through basement membranes is crucial during morphogenesis and cancer metastasis. Here, we genetically dissect this process during anchor-cell invasion into the vulval epithelium in C. elegans. We have identified the fos transcription factor ortholog fos-1 as a critical regulator of basement-membrane removal. In fos-1 mutants, the gonadal anchor cell extends cellular processes normally toward vulval cells, but these processes fail to remove the basement membranes separating the gonad from the vulval epithelium. fos-1 is expressed in the anchor cell and controls invasion cell autonomously. We have identified ZMP-1, a membrane-type matrix metalloproteinase, CDH-3, a Fat-like protocadherin, and hemicentin, a fibulin family extracellular matrix protein, as transcriptional targets of FOS-1 that promote invasion. These results reveal a key genetic network that controls basement-membrane removal during cell invasion.
细胞通过基底膜的侵袭在形态发生和癌症转移过程中至关重要。在此，我们通过遗传学方法剖析了秀丽隐杆线虫中锚定细胞侵入外阴上皮过程中的这一过程。我们已鉴定出原癌基因转录因子直系同源物fos-1是基底膜去除的关键调节因子。在fos-1突变体中，性腺锚定细胞通常会向外阴细胞正常延伸细胞突起，但这些突起无法去除将性腺与外阴上皮分隔开的基底膜。fos-1在锚定细胞中表达，并自主控制侵袭细胞。我们已鉴定出膜型基质金属蛋白酶ZMP-1、类Fat原钙黏蛋白CDH-3和纤连蛋白家族细胞外基质蛋白血纤蛋白作为促进侵袭的FOS-1转录靶点。这些结果揭示了一个控制细胞侵袭过程中基底膜去除的关键遗传网络。
