OVEREXPRESSION OF THE HYALURONAN RECEPTOR RHAMM IS TRANSFORMING AND IS ALSO REQUIRED FOR H-RAS TRANSFORMATION
OVEREXPRESSION OF THE HYALURONAN RECEPTOR RHAMM IS TRANSFORMING AND IS ALSO REQUIRED FOR H-RAS TRANSFORMATION
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DOI：
10.1016/0092-8674(95)90048-9
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发表时间：
1995-07-14
期刊：
影响因子：
64.5
通讯作者：
TURLEY, EA
中科院分区：
文献类型：
--
作者：
HALL, CL;YANG, BH;TURLEY, EA
通过将rhamm基因过表达导入成纤维细胞，可导致肺内自发性转移。转H-ras基因的纤维肉瘤中，rhamm的显性抑制突变体呈现出一种所谓的逆转表型，完全不致瘤、不转移。反之，稳定表达低水平RHAMM的成纤维细胞对RES转化有抵抗力。综上所述，这些结果表明Rhamm在Res下游起作用。RHAMM功能的丧失会破坏局灶性粘连内的信号传递，特别是局灶性粘连蛋白激酶磷酸化的改变，结果是这些局灶性粘连不能对透明质酸做出反应。这些结果为一种新的细胞外基质受体的致癌潜力提供了证据，并在ras的转化和该癌基因转化所需的焦点粘连内的信号之间建立了功能联系。
Overexpression of the RHAMM gene by transfection into fibroblasts is transforming and causes spontaneous metastases in the lung. H-ras-transformed fibrosarcomas transfected with a dominant suppressor mutant of RHAMM exhibit a so-called revertant phenotype end are completely nontumorigenic and nonmetastatic. Conversely, fibroblasts stably expressing low levels of RHAMM as a result of antisense transfection are resistant to res transformation. Collectively, these results indicate that RHAMM acts downstream of res. The loss of functional RHAMM ablates signaling within focal adhesions, in particular changes in focal adhesion kinase phosphorylation, and as a result these focal adhesions are unable to turn over in response to hyaluronan. These results provide evidence of the oncogenic potential of a novel extracellular matrix receptor and establish a functional link between transformation by ras and signaling within focal adhesions that are required for transformation by this oncogene.