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integral transmembrane protein belonging to the immunoglobulin family that par-
ticipates in cell-cell adhesion process independently of Ca
2+
and has been ascribed
with tumour suppressor function (
www.ncbi.nlm.nih.gov/gene/23705
updated 2012).
Mao et al. (2004) noticed that when re-expressed in NSCLC A549 cell line, CADM1
suppressed cell proliferation and induced caspase-mediated apoptosis and also sup-
pressed tumorigenesis in animal models. CADM1 was downregulated by promoter
methylation in many cell lines derived from human neoplasms. In NSCLC, promoter
methylation seemed to be related to state of tumour progression, with larger propor-
tion of advanced T2-T4 displaying methylation far more as compared to early T1
stage tumours (Fukami et al., 2003). In ovarian cancer, loss of CADM1 expression
markedly correlated with metastasis to lymph nodes and with the presence of distant
metastases and poorer survival (Yang et al., 2011b). Certain miRNAs have been sug-
gested to be capable of directly targeting DNA methyltransferases to downregulate
and inactivate suppressor genes. Such a mode of action has been ascribed to miRNA-
342 (Wang et al., 2011b). EPB41L3 is modulated by miRNAs. MiRNA-223 is said
to downregulate the expression of EPB41L3 by directly targeting its 3′-untranslated
regions (Li, 2011c).
It may be noted that no link has been reported between miRNAs and other estab-
lished suppressor genes including nm23, KAII and KiSS1, and the less convincingly
postulated tumour suppressor MKK4 (mitogen-activated kinase kinase 4). This is not
to say miRNAs are not involved with any of them or are not influenced by them, but
possibly not many investigators are attracted to the proposition.
Deserving much attention is the thought that in some cases, miRNAs might be
responsible for the patterns of metastatic spread encountered in human cancers. This
is implicit in the finding that RKIP (the suppressor Raf kinase inhibitory protein), a
putative metastasis suppressor discussed at another location in this topic, seems to
engage miRNA let-7 (Yun et al., 2011). They show that RKIP inhibits let-7 targets
(HMGA2, BACH1) that are able to upregulate MMP1, OPN (osteopontin), CXCR4
involved in bone metastasis.
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