Abstract
We cloned recently an alternatively spliced variant of KAI1 mRNA that lacked exon 7 at the COOH-terminal region and showed differences in metastasis suppression when compared with the wild-type KAI1. These findings indicated that the COOH-terminal region of KAI1 is critical for its metastasis suppressor function. In this study, we isolated a cDNA clone of VANGL1, a member of the tetraspanin protein family, which interacted specifically with the COOH-terminal cytoplasmic domain of KAI1 in the yeast two-hybrid system. We renamed it KAI1 COOH-terminal interacting tetraspanin (KITENIN). We found that KITENIN-overexpressing CT-26 mouse colon cancer cells showed increased tumorigenicity and early hepatic metastasis in vivo, as well as increased invasiveness and adhesion to fibronectin in vitro compared with parental cells. Moreover, increased levels of KITENIN were observed in a human gastric tumor and its metastatic tissues, compared with the normal adjacent mucosa. Our results indicate that KITENIN promotes adhesion and invasion of cancer cells in vitro and in vivo, and suggest that KITENIN participates in the regulation of the tumor formation and metastasis by interacting with KAI1, a metastasis suppressor and antisense KITENIN strategy that can be used to inhibit metastasis in various cancers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing
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Animals
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Antigens, CD*
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Division / physiology
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Cell Line, Tumor
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / pathology
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DNA, Complementary / genetics
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DNA, Complementary / isolation & purification
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Extracellular Matrix / metabolism
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Genes, Tumor Suppressor
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Humans
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Kangai-1 Protein
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Liver Neoplasms, Experimental / genetics
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Liver Neoplasms, Experimental / metabolism*
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Liver Neoplasms, Experimental / secondary
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred BALB C
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Neoplasm Metastasis
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Proto-Oncogene Proteins*
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Stomach Neoplasms / genetics
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Stomach Neoplasms / metabolism*
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Stomach Neoplasms / pathology
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Tetraspanins
Substances
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Antigens, CD
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Biomarkers, Tumor
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CD82 protein, human
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Carrier Proteins
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Cd82 antigen, mouse
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DNA, Complementary
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Kangai-1 Protein
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Membrane Glycoproteins
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Membrane Proteins
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Proto-Oncogene Proteins
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TSPAN4 protein, human
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Tetraspanins
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VANGL1 protein, human