Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation.
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.
Hall
C L
CL
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Yang
B
B
Yang
X
X
Zhang
S
S
Turley
M
M
Samuel
S
S
Lange
L A
LA
Wang
C
C
Curpen
G D
GD
Savani
R C
RC
Greenberg
A H
AH
Turley
E A
EA
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts; D005354:Fibrosarcoma / Q000473:pathology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015870:Gene Expression; D011905:Genes, ras / Q000502:physiology*; D018960:Hyaluronan Receptors; D008168:Lung / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D016372:RNA, Antisense; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013489:Suppression, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D016372:RNA, Antisense; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse