Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK.
A human fibroblast cDNA expression library was screened for cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH 3T3 cells. One such gene, RECK, encodes a membrane-anchored glycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains. While RECK mRNA is expressed in various human tissues and untransformed cells, it is undetectable in tumor-derived cell lines and oncogenically transformed cells. Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK may link oncogenic signals to tumor invasion and metastasis.
Takahashi
C
C
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Sheng
Z
Z
Horan
T P
TP
Kitayama
H
H
Maki
M
M
Hitomi
K
K
Kitaura
Y
Y
Takai
S
S
Sasahara
R M
RM
Horimoto
A
A
Ikawa
Y
Y
Ratzkin
B J
BJ
Arakawa
T
T
Noda
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics*; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D011905:Genes, ras; D006801:Humans; D008207:Lymphatic Metastasis; D020780:Matrix Metalloproteinase 9; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D009857:Oncogenes; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D018076:DNA, Complementary; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; C492025:Reck protein, mouse; D017364:Collagenases; D020780:Matrix Metalloproteinase 9