The Molecular Biology of Brain Metastasis

Table 2

Representative metastasis and invasion suppressor genes.

Gene	Cancer/metastatic tumor	Function(s) of protein	OMIM no.	Chromosome Location
NM23	Breast, colon, melanoma	A histidine kinase. Nm23 phosphorylates KSR and can lead to decreased ERK 1/2 activation. appears to play a role in normal development and differentiation	156490	17q21.3
MKK4	Breast, ovarian, and prostate	A mitogen-activated protein kinase (MAPKK) that phosphorylates p38 and Jun (JNK) kinases	601335	17p11.2
BRMS1	Breast, melanoma	Functions in gap-junction communication	606259	11q13.1-q13.2
KiSS1	Breast, melanoma	A G-protein coupled receptor ligand, also known as metastin.	603286	1q32
KAI1 (CD82)	Bladder, breast, lung, pancreas, and prostate	Interact with beta-catenin-reptin and histone deacetylases. It may desensitize EGFR activity, also known as kangai	600623	11p11.2
CD44	Breast, colon, lung, melanoma, prostate	An integral cell membrane glycoprotein that affects cell adhesion. Decreased expression due in part to hypermethylation	107269	11pter-p13
CRSP3	Melanoma	A transcriptional coactivator that may work through the enhancer binding factor Sp1	605042
RHOGDI2	Bladder, breast, colon, kidney, liver, lung, and prostate	Regulates function of Rho and Rac, GTP-binding proteins of the Ras superfamily		11p11.2
VDUP1	Melanoma	A differentiation factor via thioredoxin inhibition	606599	1q21
PTEN/MMAC1	Breast, colon, endometrial, germ cell, kidney, lung, melanoma, and thyroid	A homologue of cytoskeletal tension, leading to invasion and metastasis through interaction with actin filaments at focal adhesions	601728	10q23.31
VHL	Renal cell, pheochromocytoma, and hemangioblastoma	Encodes protein products playing an essential role in microtubule stability, orientation, tumor suppression, cilia formation, signaling of cytokines, and extracellular matrix assembly	608537	3p25.3
TIMP2	Melanoma	Protease inhibitor plays a role in preventing excessive ECM disruption	188825	17q25.3
SMAD4	Pancreatic cancer, colorectal, and prostate	Transcription factor, pivotal role in signal transduction of TGFβ	600993	18q21.2
RRM1	Lung	Cell cycle regulator	180410	11p15.4
PTPN11	Lung, colon, thyroid, and melanoma	Regulates tyrosine phosphatase, proliferation, differentiation, motility, and apoptosis of cells	176876	12q24.1
CDH1	Gastric, breast	Cellular adherens junctional protein	192090	16q22.1
CASP8	Gastric, breast, lung, and PNETs	Apoptotic cascade via aspartate-specific cysteine proteases	601763	2q33

Definitions: EGFR: epidermal growth factor; ERK: extracellular signal-regulated kinase; JNK: Jun-terminal kinase; KSR: kinase suppressor of Ras. OMIM no.: Online Mendelian Inheritance in Man Identification number (http://www.ncbi.nlm.nih.gov/), which provides detailed information and references for these genes, their protein products, and potential functions.