FOS-1 promotes basement-membrane removal during anchor-cell invasion in C. elegans

FOS-1 promotes basement-membrane removal during anchor-cell invasion in C. elegans
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DOI:
10.1016/j.cell.2005.03.031
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发表时间:
2005-06-17
期刊:
影响因子:
64.5
通讯作者:
Sternberg, PW
Sternberg, PW
中科院分区:
生物学1区
文献类型:
--
作者:
Sherwood, DR;Butler, JA;Sternberg, PW

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细胞通过基底膜的侵袭在形态发生和癌转移过程中是至关重要的。在这里,我们从遗传学角度剖析了锚细胞侵入C。优雅的。我们已经确定了fos转录因子的直系同源物fos-1作为一个重要的调节基底膜去除。在fos-1突变体中,性腺锚细胞正常地向外阴细胞延伸细胞突起,但是这些突起不能去除将性腺与外阴上皮分离的基底膜。fos-1在锚细胞中表达,自主控制侵袭细胞。我们已经确定了ZMP-1,一种膜型基质金属蛋白酶,CDH-3,一种脂肪样原钙粘蛋白,和hemictin,一种纤维蛋白家族细胞外基质蛋白,作为FOS-1的转录靶点,促进侵袭。这些结果揭示了一个关键的遗传网络,控制基底膜去除细胞入侵。
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.