KAI1 COOH-terminal interacting tetraspanin (KITENIN), a member of the tetraspanin family, interacts with KAI1, a tumor metastasis suppressor, and enhances metastasis of cancer

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 suppre...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2004-06, Vol.64 (12), p.4235-4243
Main Authors: JI HEE LEE, SEI RYUN PARK, CHAY, Kee-Oh, SEO, Young-Woo, KOOK, Hyun, KYU YOUN AHN, YOUNG JIN KIM, KYUNG KEUN KIM
Format: Article
Language:English
Subjects:
Alternative Splicing
Animals
Antigens, CD
Antineoplastic agents
Biological and medical sciences
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Carrier Proteins - biosynthesis
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Division - physiology
Cell Line, Tumor
Colonic Neoplasms - genetics
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
DNA, Complementary - genetics
DNA, Complementary - isolation & purification
Extracellular Matrix - metabolism
Genes, Tumor Suppressor
Humans
Kangai-1 Protein
Liver Neoplasms, Experimental - genetics
Liver Neoplasms, Experimental - metabolism
Liver Neoplasms, Experimental - secondary
Medical sciences
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Membrane Proteins - isolation & purification
Membrane Proteins - metabolism
Mice
Mice, Inbred BALB C
Neoplasm Metastasis
Pharmacology. Drug treatments
Proto-Oncogene Proteins
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Tetraspanins
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-04-0275