Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation

Christine L. Hall, Baihua Yang, Xuiwei Yang, Shiwen Zhang, Maureen Turley, Shanti Samuel, Laurie A. Lange, Chao Wang, Genevieve D. Curpen, Rashmin C. Savani, Arnold H. Greenberg, Eva A. Turley

Research output: Contribution to journalArticle

247 Scopus citations

Abstract

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 and are completely nontumorigenic and nonmetastatic. Conversely, fibroblasts stably expressing low levels of RHAMM as a result of antisense transfection are resistant to ras transformation. Collectively, these results indicate that RHAMM acts downstream of ras. 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.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalCell
Volume82
Issue number1
DOIs
StatePublished - Jul 14 1995

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hall, C. L., Yang, B., Yang, X., Zhang, S., Turley, M., Samuel, S., Lange, L. A., Wang, C., Curpen, G. D., Savani, R. C., Greenberg, A. H., & Turley, E. A. (1995). Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation. Cell, 82(1), 19-28. https://doi.org/10.1016/0092-8674(95)90048-9