Dissecting the diverse functions of the metastasis suppressor CD82/KAI1

Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States.
FEBS letters (Impact Factor: 3.17). 08/2011; 585(20):3166-73. DOI: 10.1016/j.febslet.2011.08.031
Source: PubMed


The recent identification of metastasis suppressor genes, the products of which inhibit metastasis but not primary tumor growth, distinguishes oncogenic transformation and tumor suppression from a hallmark of malignancy, the ability of cancer cells to invade sites distant from the primary tumor. The metastasis suppressor CD82/KAI1 is a member of the tetraspanin superfamily of glycoproteins. CD82 suppresses metastasis by multiple mechanisms including inhibition of cell motility and invasion, promotion of cell polarity as well as induction of senescence and apoptosis in response to extracellular stimuli. A common feature of these diverse effects is CD82 regulation of membrane organization as well as protein trafficking and interactions, which affects cellular signaling and intercellular communication.

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    • "Among them, the tumor suppressor CD82 was up-regulated by WT EGFR but down-regulated by mutant EGFRs, which is intriguing. CD82, a member of the teraspanin family, is a cancer metastasis suppressor and is often down-regulated in cancers [15] [16] [17] [18]. Moreover, CD82 expression is correlated with a good prognosis in non-small cell lung cancer (NSCLC) patients [19]. "
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    • "Expression of MSGs is frequently reduced in highly metastatic tumor cells [6]. The MSG KAI1 has previously been shown to interfere with multiple steps of the metastatic cascade, including proliferation, invasion, and migration, making it an attractive marker to evaluate in UM and other cancers [7] [8]. Multiple studies have demonstrated that the expression of KAI1 in some primary tumor types is inversely correlated with formation of metastasis [9]. "
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    ABSTRACT: Introduction. Uveal melanoma (UM) is an intraocular tumor that leads to metastatic disease in approximately 50% of afflicted patients. There is no efficacious treatment for metastatic disease in this cancer. Identification of markers that can offer prognostic and therapeutic value is a major focus in this field at present. KAI1 is a metastasis suppressor gene that has been reported to play a role in various human malignancies, although it has not previously been evaluated in UM. Purpose. To investigate the expression of KAI1 in UM and its potential value as a prognostic marker. Materials and Methods. 18 cases of human primary UM were collected and immunostained for KAI1 expression. A pathologist evaluated staining intensity and distribution semiquantitatively. Each case was categorized as group 1 (low staining) or group 2 (high staining). Results. In group 2, two of the 12 cases presented with metastasis. Conversely, in group 1, five out of 6 cases had metastasis. The mean follow-up of patients who did not develop metastasis was 81.81 months (median: 75 months) versus 42.14 months (median: 44 months) for patients with metastasis. Conclusions. KAI1 is a promising candidate marker that may offer prognostic value in UM; it may also represent a therapeutic target in metastatic disease.
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    • "The specific function of these three markers in monocytes is not well defined to date. CD82 is a glycoprotein that belongs to the tetraspanin superfamily and is known as a metastasis suppressor [30]. As other tetraspanins, CD82 is involved in the regulation of membrane dynamic and protein trafficking in cell membranes. "
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