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

doi:10.1016/0092-8674(95)90048-9

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

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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 language	English (US)
Pages (from-to)	19-28
Number of pages	10
Journal	Cell
Volume	82
Issue number	1
DOIs	https://doi.org/10.1016/0092-8674(95)90048-9
State	Published - Jul 14 1995

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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@article{8bbece29b6ca4bc89c7639c4666ef713,

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

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.",

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

note = "Funding Information: This work was supported by National Cancer Institute of Canada (NCIC), Medical Research Council (MRC), and Hyal Pharmaceutical grants to E. A. T.; C. H. was supported by an MRC Studentship, B. Y. by a Manitoba Health Research Council Fellowship, and S. S. by an NCIC Fellowship. A. H. G. is a Terry Fox Scientist of the NCIC, and E. A. T. is a Children{\textquoteright}s Hospital Research Foundation Scholar.",

year = "1995",

month = jul,

day = "14",

doi = "10.1016/0092-8674(95)90048-9",

language = "English (US)",

volume = "82",

pages = "19--28",

journal = "Cell",

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TY - JOUR

T1 - Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation

AU - Hall, Christine L.

AU - Yang, Baihua

AU - Yang, Xuiwei

AU - Zhang, Shiwen

AU - Turley, Maureen

AU - Samuel, Shanti

AU - Lange, Laurie A.

AU - Wang, Chao

AU - Curpen, Genevieve D.

AU - Savani, Rashmin C.

AU - Greenberg, Arnold H.

AU - Turley, Eva A.

N1 - Funding Information: This work was supported by National Cancer Institute of Canada (NCIC), Medical Research Council (MRC), and Hyal Pharmaceutical grants to E. A. T.; C. H. was supported by an MRC Studentship, B. Y. by a Manitoba Health Research Council Fellowship, and S. S. by an NCIC Fellowship. A. H. G. is a Terry Fox Scientist of the NCIC, and E. A. T. is a Children’s Hospital Research Foundation Scholar.

PY - 1995/7/14

Y1 - 1995/7/14

N2 - 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.

AB - 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.

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

Abstract

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