Tetraspanin CD151 Promotes Cell Migration by Regulating Integrin Trafficking

Liu, Li; He, Bo; Liu, Wei M.; Zhou, Dongming; Cox, John V.; Zhang, Xin A.

doi:10.1074/jbc.m701165200

Cited by 127 publications

(140 citation statements)

References 63 publications

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“…Adhesion strengthening via laminin-binding integrins has been shown to depend on CD151 (44).The promigratory role of CD151 may depend, in part, on its regulation of integrin internalization and trafficking (16,45). Sadej and colleagues (23) reported that KD of CD151 depleted TGF-b-induced scattering of breast cancer cells in 3-dimensional culture.…”

Section: Discussionmentioning

confidence: 99%

Genetic Ablation of the Tetraspanin CD151 Reduces Spontaneous Metastatic Spread of Prostate Cancer in the TRAMP Model

Copeland

Bowman

Ashman

2013

Molecular Cancer Research

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Tetraspanins are integral membrane proteins that associate with motility-related molecules such as integrins. Experimental studies have indicated that they may be important regulators of tumor invasion and metastasis, and high expression of the tetraspanin CD151 has been linked to poor prognosis in a number of cancers. Here, we show for the first time that genetic ablation of CD151 inhibits spontaneous metastasis in a transgenic mouse model of de novo tumorigenesis. To evaluate the effects of CD151 on de novo prostate cancer initiation and metastasis, a Cd151 À/À (KO) murine model was crossed with the Transgenic Adenocarcinoma of MouseProstate (TRAMP) model. Mice were analyzed for initiation of prostate tumor by palpation and primary tumors were analyzed by immunohistochemistry. Liver and lungs were examined for incidence and size of spontaneous metastatic lesions by histopathology. Knocking-out Cd151 had no significant effect on prostate cancer initiation or on expression of markers of proliferation, apoptosis, or angiogenesis in primary tumors. However, it did significantly decrease metastasis in a site-specific fashion, notably to the lungs but not the liver. Thus, CD151 acts principally as promoter of metastasis in this model. Prostate cancer is the second highest cause of cancerrelated deaths in men in most Western countries, with the majority of deaths attributed to late-stage metastatic disease. CD151 may prove to be a valuable prognostic marker for treatment stratification and is a possible antimetastatic target. Mol Cancer Res; 11(1); 95-105. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

Genetic Ablation of the Tetraspanin CD151 Reduces Spontaneous Metastatic Spread of Prostate Cancer in the TRAMP Model

Copeland

Bowman

Ashman

2013

Molecular Cancer Research

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“…19,20 In terms of the latter, integrins can enter caveolae followed by an internalization route that is regulated by protein kinase Ca and dynamin. 21 Since we found that MIA protein uptake into cells that were treated with G € O6976 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Processing of MIA protein during melanoma cell migration

Schmidt

Bosserhoff

2009

Intl Journal of Cancer

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MIA (melanoma inhibitory activity) protein, identified as a small 11 kDa protein highly expressed and secreted by malignant melanoma cells, plays an important functional role in melanoma development, progression and tumor cell invasion. Recent data describe a direct interaction of MIA protein with cell adhesion receptors integrin a 4 b 1 and integrin a 5 b 1 and extracellular matrix molecules. By modulating integrin activity MIA protein mediates detachment of melanoma cells from surrounding structures resulting in enhanced invasive and migratory potential. However, until today a detailed understanding of the processes of MIA function is missing. In this study, we show that after binding of MIA protein to integrin a 5 b 1 , MIA protein is internalized together with this cell adhesion receptor at the cell rear. This mechanism enables tumor cells to migrate in a defined direction as appropriate for invasion processes. Treatment of melanoma cells with PKC-inhibitors strongly reduced internalization of MIA protein. Endocytosis is followed by dissociation of MIA-integrin complexes. In acidic vesicles MIA protein is degraded while integrins are recycled. Treatment of melanoma cells with MIA inhibitory peptides almost completely blocked the MIA protein uptake into cells. As MIA protein has a major contribution to the aggressive characteristics of malignant melanoma in particular to formation of metastasis, it is important to elucidate the MIA functional mechanism in tumor cells to find novel therapeutic strategies in the fight against skin cancer. ' 2009 UICC Key words: melanoma; MIA; endocytosis; migration; integrin Malignant melanoma is characterized by aggressive local growth and early formation of metastasis, and accounts for 75 percent of deaths associated with skin cancer. Previously, melanoma inhibitory activity (MIA) has been identified as an 11 kDa protein strongly expressed and secreted by malignant melanoma cells but not expressed in melanocytes.1 Subsequent in vitro and in vivo experiments revealed that MIA protein plays an important functional role in melanoma development and cell invasion, 2 hence MIA expression levels parallel closely the capability of melanoma cells to form metastases in syngeneic animals.3,4 Increased MIA serum concentrations serve as a reliable clinical tumor marker to detect and monitor metastatic diseases in patients with malignant melanomas. 1,5,6 The three-dimensional structure of the protein was solved by multidimensional nuclear magnetic resonance (NMR) 7-9 and Xray crystallography techniques. 10 Corresponding data indicate that MIA defines a novel type of secreted protein: the MIA protein family, consisting of MIA and the homologous proteins OTOR, MIA-2 and TANGO (MIA-3). The MIA protein family is the first family of secreted proteins comprising an SH3 domain-like fold in solution.11 Furthermore, phage display experiments and NMR spectra revealed that MIA protein interacts with peptides matching to extracellular matrix proteins including human fibronectin type III repeats and la...

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“…Other tetraspanins have been shown to regulate early biosynthesis of their associated molecules. Examples include CD151/ α3β1 [119,120], uroplakins/UPs [121], CD81/CD19 [122], and CD9/pre-β1 integrin [123]. In one report, re-expression of CD82 in tumor cells negatively influenced pre-β1 integrin processing resulting in reduced β1 integrin on the cell surface [124].…”

Section: Integrin Traffickingmentioning

confidence: 99%

“…A direct interaction between the α3 and α6 integrins and CD151 was demonstrated by their ability to be chemically cross-linked, stability of the association in harsh detergents, and identification of the interacting domains by mutagenesis [119,120,125]. CD151 interacts with the extracellular stalk domain of α3 (aa 570-705), a region not directly involved in mediating cell adhesion [125].…”

Section: Integrins Vs Tetraspaninsmentioning

confidence: 99%

Mechanisms of KAI1/CD82-Induced Prostate Cancer Metastasis

Miranti¹

2011

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:5f. WORK UNIT NUMBER Mechanisms of KAI1/CD82-Induced Prostate Cancer Metastasis Cynthia Miranti Metastatic prostate cancer kills over 28,000 American men every year. The mechanisms that drive metastasis are poorly understood. We investigated the hypothesis that loss of the metastasis suppressor gene, CD82/KAI1 in primary prostate tumors of genetically engineered mice would be sufficient to induce metastasis. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTWhile CD82 was sufficient to suppress metastasis of metastatic tumor cells lines and did so by repressing c-Met, the reverse was not true, i.e. loss of CD82 was not sufficient to induce metastasis. This was the case in at least two genetically engineered prostate cancer models. Ongoing studies in different models may yet prove otherwise.Our other hypothesis, that CD82 was suppressing c-Met and invasion through integrins, was proven invalid in these studies. Other tetraspanins that CD82 associates with, i.e. CD9 and CD151 were required to suppress cMet, but not invasion. Thus, these two events must be occurring via different mechanisms. Nonetheless, we are finding several interesting phenotypes in the CD82 null mice which will shed additional light on CD82 function overall and be useful in developing new hypotheses about how CD82 functions as a metastasis suppressor. cell biology, integrins, KAI1/CD82, tetraspanins, metastasis, c-Met, HGF, mouse models cindy.miranti@vai.org 3 INTRODUCTIONProstate cancer is the most frequently diagnosed cancer and the third leading cause of cancer deaths in men in the United States. 1 Death is due to invasion and metastasis beyond the prostate gla...

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Tetraspanin CD151 Promotes Cell Migration by Regulating Integrin Trafficking

Cited by 127 publications

References 63 publications

Genetic Ablation of the Tetraspanin CD151 Reduces Spontaneous Metastatic Spread of Prostate Cancer in the TRAMP Model

Genetic Ablation of the Tetraspanin CD151 Reduces Spontaneous Metastatic Spread of Prostate Cancer in the TRAMP Model

Processing of MIA protein during melanoma cell migration

Mechanisms of KAI1/CD82-Induced Prostate Cancer Metastasis

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