Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RECK was first isolated as a transformation suppressor gene by cDNA expression cloning in a mouse fibroblast cell line transformed by an activated RAS oncogene. Subsequently, reduced expression of RECK in transformed cells and cancer cells were demonstrated. Moreover, in several types of tumors, positive correlation between RECK expression and survival of patients have been noted. RECK encodes a GPI-anchored glycoprotein harboring three protease inhibitor-like domains. The RECK protein regulates at least three members of the matrix metalloproteinase (MMP) family, MMP-2, MMP-9, and MT1-MMP, in vitro or in cultured cells. Restored expression of RECK in cancer cell lines results in strong suppression of invasion, metastasis, and tumor angiogenesis. Mice lacking RECK die in utero with reduced integrity of blood vessels, the neural tube, and mesenchymal tissues. In these mice, MMP activity is elevated, and the amount of collagen type I greatly reduced. The RECK null phenotype is partially rescued (half day delay of death and marked recovery of tissue integrity) by MMP-2 null mutation, demonstrating functional interaction between RECK and MMP-2 in vivo and involvement of other target(s) for RECK in the lethal phenotype. These findings indicate that (i) RECK is an important regulator of extracellular matrix remodeling and that (ii) down-regulation of RECK by oncogenic signaling leads to the excessive activation of MMPs thereby promoting malignant behavior of cancer cells such as invasion, metastasis, and angiogenesis.
Cancer Metastasis Rev
PMID:RECK: a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. 1278 95

Patient prognosis in colorectal cancer is determined as in most solid cancers by the extent of local invasion and the presence of lymph node and distant metastases. The invasive potential of a tumor depends on the ability to degrade extracellular matrix proteins, for example, by matrix metalloproteinases. An important inhibitor of matrix metalloproteinases is reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a membrane-anchored glycoprotein. This study investigated the prognostic relevance of RECK expression in colorectal cancer in a cohort of 283 patients. Analysis of immunohistochemical tissue microarray data showed that RECK protein levels did not seem to correlate with clinicopathologic parameters (Spearman rank correlation coefficients between -0.14 and -0.18) and that decreased RECK expression was an independent prognostic factor of poor survival, with a mean survival of 70 months in RECK-negative (146 cases) versus 97 months in RECK-positive patients (137 cases) (log-rank test, P = .002).
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PMID:Reversion-inducing cysteine-rich protein with Kazal motif (RECK) expression: an independent prognostic marker of survival in colorectal cancer. 2239 71