81839

VANGL1

VANGL planar cell polarity protein 1;VANGL1;VANGL planar cell polarity protein 1

KAI1 C-terminal interacting tetraspanin|loop-tail protein 2 homolog|strabismus 2|van Gogh-like protein 1|vang-like 1 (van gogh, Drosophila)|vang-like protein 1

1p13.1

protein-coding

By analyzing public data sets of gene expression in human breast cancers we observed that increased levels of transcripts encoding the planar cell polarity (PCP) proteins SCRIB and VANGL1 correlate with increased risk of patient relapse. Experimentally, we found that reducing expression of SCRIB by short-hairpin RNAs (shRNAs) reduces the growth of human breast cancer cells in xenograft assays. To investigate SCRIB-associated proteins that might participate in the responses of breast cancer cells to altered levels of SCRIB, we used mass spectrometry and confocal microscopy. These studies reveal that SCRIB is present in at least two unique protein complexes: (1) a complex of SCRIB, ARHGEF, GIT and PAK (p21-activated kinase), and (2) a complex of SCRIB, NOS1AP and VANGL. Focusing on NOS1AP, we observed that NOS1AP colocalizes with both SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells, but does not colocalize with either SCRIB or VANGL1 at cell junctions in normal breast cells. We investigated the effects of shRNA-mediated knockdown of NOS1AP and SCRIB in vitro, and found that reducing NOS1AP and SCRIB slows breast cancer cell migration and prevents the establishment of leading-trailing polarity. We also find that reduction of NOS1AP enhances anchorage-independent growth. Collectively these data point to the relevance of NOS1AP and SCRIB protein complexes in breast cancer.

KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor invasion and metastasis in various cancers. The aim of current study was to evaluate whether KITENIN affects tumor cell invasion and prognosis in human colorectal cancers. We investigated the biologic role of KITENIN on tumor cell invasion by using small interfering RNA in Caco2, DLD1, and SW480. We evaluated the expression of KITENIN and activator protein-1 (AP-1) target genes in human colorectal cancer tissues. The tumor cell invasion was decreased by knockdown of KITENIN in three tested cell lines. The mRNA expression of cyclin D1 and COX-2 was decreased in KITENIN knockdown Caco2 and the mRNA expression of MMP-3 and COX-2 was decreased in KITENIN knockdown DLD1 and SW480. The extracellular-signal protein kinase 1/2 (ERK1/2) phosphorylation was decreased in KITENIN knockdown in three tested cell lines. expression of KITENIN and AP-1 target genes was significantly increased in human colorectal cancer tissues. The ERK1/2, c-Jun N-terminal kinase (JNK) and p38 phosphorylations were increased in human colorectal cancer tissues. expression of KITENIN was significantly associated with lymphovascular invasion, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN is associated with human colorectal cancer progression including invasion and metastasis.

KAI1 C-terminal interacting tetraspanin (KITENIN) is reported to promote metastasis in mouse colon cancer models. We investigated the role of KITENIN on the progression of squamous cell carcinoma (SCC). In a preliminary clinical study using resected tissues from head and neck SCC patients, KITENIN was highly expressed in tumors and metastatic lymph nodes, while KAI1 was more increased in adjacent mucosa than in tumor. KITENIN-transfected mouse squamous cancer (SCC VII/KITENIN) cells showed significantly higher invasion, migration, and proliferation than empty vector-transfected cells. In syngeneic mouse squamous tumor models, more increased tumor volume and enhanced lung metastasis were found in SCC VII/KITENIN cells-injected mice. Thus, KITENIN increases invasion and migration of squamous cancer cells and thereby promotes distant metastasis in mouse squamous tumor models.

OBJECTIVE: KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor invasion and metastasis in various cancers. The aim of this study was to investigate expression of KITENIN in patients with oral cavity squamous cell carcinoma (SCC) and to determine whether KITENIN affects tumor cell behavior in oral cavity SCC cell line. METHODS: Western blotting and immunohistochemistry was used to assess alteration of KITENIN expression in human oral cavity SCC and normal oral cavity mucosa. To evaluate the impact of KITENIN knockdown, the cell invasion assay and cell migration assay using small-interfering RNA were performed. RESULTS: KITENIN protein expression was significantly increased in human oral cavity SCC tissues than in normal oral cavity mucosa by Western blotting. KITENIN immunoreactivity was strongly identified in human oral cavity SCC relative to adjacent normal tissue. Knockdown of KITENIN resulted in significantly reduced cell invasion in human oral cavity SCC cells (p=0.001). Cell migration showed a marked decrease in KITENIN knockdown oral cavity SCC cells compared to the negative control oral cavity SCC cells (p=0.01). CONCLUSION: KITENIN is associated with tumor invasiveness and metastasis in human oral cavity SCC.