Metastasis Suppressor KAI1/CD82 Attenuates the Matrix Adhesion of Human Prostate Cancer Cells by Suppressing Fibronectin Expression and β &lt;sub&gt;1&lt;/sub&gt; Integrin Activation

Lee, Hyunah; Park, Iha; Byun, Hee-Jung; Jeoung, Dooil; Kim, Young‐Myeong; Lee, Hansoo

doi:10.1159/000329979

Cited by 45 publications

(40 citation statements)

References 44 publications

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“…Increasing attention has been paid to the interaction between different factors involved in metastatic processes in hormone-sensitive tumors [22][23][24]. To our knowledge, this is the first study which has analyzed the association between steroid receptors, KAI1 protein, MMP-2, and MMP-9 -as well as between KAI1, MMP-2, and MMP-9 Table 3.…”

Section: Discussionmentioning

confidence: 99%

The relationships between the immunoexpression of KAI1, MMP-2, MMP-9 and steroid receptors expression in endometrial cancer

Gryboś

Bär

2014

Folia Histochem Cytobiol.

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Abstract:The role of the parallel expression of the KAI1 protein and metalloproteinases (MMP-2 and MMP-9) in respect to the status of steroid receptors in endometrial cancer is still incompletely understood. The aim of this study was to evaluate the expression of and correlation between KAI1 on one hand and MMP-2 and MMP-9 on the other hand in terms of the status of the estrogen (ER) and progesterone receptors (PR) in 100 patients with endometrial cancer. The expressions of KAI1, MMP-2, MMP-9, ER and PR were assessed immunohistochemically on paraffin-embedded tissues. No correlations were found between these biomarkers and the clinical and pathological parameters of the endometrial cancer. However, in KAI1-positive cases, the expression was limited to a small area of tumor tissue in FIGO stages III-IV. A tendency towards the high expression of MMP-9 and MMP-2 was observed in the advanced stages of endometrial cancer (FIGO IIIA-IV). Positive correlations between the presence of KAI1 and PR and between the presence of MMP-9 and PR were found in endometrial cancer. A positive correlation was also observed between KAI1 and MMP-2 expression, and a borderline one between KAI1 and MMP-9 expression in endometrial cancer. KAI1 -/MMP-2 + and KAI1 -/MMP-9 + phenotypes were more often observed in FIGO stage II. Our study showed that KAI1 protein, as well as steroid receptors, might modulate MMP-2 and MMP-9 expression in endometrial cancer. Our study revealed that the overlapping expression of the biomarkers investigated here suggests that cooperation between these molecules exists, even at the early stages of endometrial cancer growth, and may determine the speed of tumor cell dissemination and might characterize the biological behavior of endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

The relationships between the immunoexpression of KAI1, MMP-2, MMP-9 and steroid receptors expression in endometrial cancer

Gryboś

Bär

2014

Folia Histochem Cytobiol.

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“…Down-regulation of KAI1 expression was associated with advanced stages of many malignancies including prostate, colon, lung, pancreatic, breast, ovarian and other cancers (6,7). KAI1 belongs to transmembrane 4 superfamily (TM4SF), encoding a 267 amino acid glycosylated membrane protein with four highly conserved transmembrane domain.…”

Section: Introductionmentioning

confidence: 99%

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

et al. 2016

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Background:The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in malignant progression of lung cancer. However, the underlying mechanism of anti-metastasis role of KAI1 in lung cancer is hardly known. In this paper, we sought to study the function and regulatory mechanism of KAI1 in high metastasis lung cancer cell line.Methods: KAI1 expression was detected in high/low metastatic large lung cancer cell line L9981/NL9980 by quantitative real-time polymerase chain reaction (qRT-PCR). The tumor suppressor function of KAI1 was determined by wound healing assay after over-expression or knockdown of KAI1 in L9981 or NL9980 cells.Invasion assay was performed to detect the invasion ability of L9981 by transfection of KAI1. The effect of tumor suppressor p53 on KAI1 expression was measured by western blot and luciferase assay. Then the regulation of KAI1 due to over-expression of metastasis suppressor nm23-H1 was monitored by qRT-PCR, western blot and reporter gene assay. The progression of L9981 cells after p53 and nm23-H1 expression was detected by invasion assay. Also, methylation status of KAI1 promoter in NL9980 and L9981 cells were examined by bisulfite sequencing and methylation-specific PCR.Results: We found that KAI1 is down-regulated in high metastatic L9981 cells compare with NL9980 cells. The migration and invasion of L9981 cells were remarkably suppressed in vitro by KAI1 transfection.The migration ability of NL9980 was enhanced by inhibition of KAI1. Furthermore, KAI1 expression was induced after over-expression of p53 or nm23-H1, while cell invasion was inhibited in L9981 cells. The results of reporter analysis indicated that KAI1 promoter region between −922 to −846 could response to nm23-H1. In addition, we discovered only slight methylation of KAI1 promoter, which showed that loss expression of KAI1 in L9981 cells may not due to promoter methylation. Conclusions:The results suggested that nm23-H1 was involved in the KAI1-regulated inhibition of metastasis in lung cancer cells. More insights into the relationship between KAI1 and other metastasis suppressors will pave the way for the elucidation of anti-metastasis mechanism in lung cancer.

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“…45 Subsequent studies have suggested that the antimetastatic effects of CD82 are mediated by inhibition of integrin-dependent activation of c-Met and Src kinases as well as suppression of fibronectin expression and b1 integrin activation. [46][47][48] Other studies have shown that CD82 inhibits Tetraspanins are composed of 4 transmembrane domains (pink), a small (EC1) and a large extracellular domain (EC2), a very small intracellular domain, and short cytoplasmic N-and C-terminal tails. The EC2 contains a variable region presenting a conserved Cys-Cys-Gly (CCG) motif and 2-6 additional cysteine residues, which form intramolecular disulfide bonds (red dotted lines).…”

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confidence: 99%

Tetraspanins in Cell Migration

Jiang¹,

Zhang

Huang

2015

Cell Adhesion & Migration

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mitogen-activated protein kinase; HCC, hepatocellular carcinoma; cdc42, cell division control protein 42; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; Sprouty2, Sprouty homolog 2; ROCK, Rho-associated protein kinase; PI3K, phosphatidylinositol-4, 5-bisphosphate 3-kinase; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; eNOS, endothelial nitric oxide synthase; HUVECs, human umbilical vein endothelial cells.Tetraspanins are a superfamily of small transmembrane proteins that are expressed in almost all eukaryotic cells. Through interacting with one another and with other membrane and intracellular proteins, tetraspanins regulate a wide range of proteins such as integrins, cell surface receptors, and signaling molecules, and thereby engage in diverse cellular processes ranging from cell adhesion and migration to proliferation and differentiation. In particular, tetraspanins modulate the function of proteins involved in all determining factors of cell migration including cell-cell adhesion, cell-ECM adhesion, cytoskeletal protrusion/ contraction, and proteolytic ECM remodeling. We herein provide a brief overview of collective in vitro and in vivo studies of tetraspanins to illustrate their regulatory functions in the migration and trafficking of cancer cells, vascular endothelial cells, skin cells (keratinocytes and fibroblasts), and leukocytes. We also discuss the involvement of tetraspanins in various pathologic and remedial processes that rely on cell migration and their potential value as targets for therapeutic intervention.

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Metastasis Suppressor KAI1/CD82 Attenuates the Matrix Adhesion of Human Prostate Cancer Cells by Suppressing Fibronectin Expression and β <sub>1</sub> Integrin Activation

Cited by 45 publications

References 44 publications

The relationships between the immunoexpression of KAI1, MMP-2, MMP-9 and steroid receptors expression in endometrial cancer

The relationships between the immunoexpression of KAI1, MMP-2, MMP-9 and steroid receptors expression in endometrial cancer

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

Tetraspanins in Cell Migration

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