OVEREXPRESSION OF THE HYALURONAN RECEPTOR RHAMM IS TRANSFORMING AND IS ALSO REQUIRED FOR H-RAS TRANSFORMATION

被引:266
作者
HALL, CL [1 ]
YANG, BH [1 ]
YANG, XW [1 ]
ZHANG, SW [1 ]
TURLEY, M [1 ]
SAMUEL, S [1 ]
LANGE, LA [1 ]
WANG, C [1 ]
CURPEN, GD [1 ]
SAVANI, RC [1 ]
GREENBERG, AH [1 ]
TURLEY, EA [1 ]
机构
[1] UNIV MANITOBA, DEPT PEDIAT, WINNIPEG, MB R3E 0V9, CANADA
基金
英国医学研究理事会;
关键词
D O I
10.1016/0092-8674(95)90048-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:19 / 28
页数:10
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