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CLCP1 interacts with semaphorin 4B and regulates motility of lung cancer cells

Oncogene volume 26, pages 4025–4031 (2007)Cite this article

Abstract

We previously established a highly metastatic subline, LNM35, from the NCI-H460 lung cancer cell line, and demonstrated upregulation of a novel gene, CLCP1 (CUB, LCCL-homology, coagulation factor V/VIII homology domains protein), in LNM35 and lung cancer specimens. In this study, we focused on the potential roles of that gene in cancer metastasis. First, we established stable LNM35 RNAi clones, in which CLCP1 expression was suppressed by RNAi, and found that their motility was significantly reduced, although growth rates were not changed. Next, in vitro selection of a phage display library demonstrated that a phage clone displaying a peptide similar to a sequence within the Sema domain of semaphorin 4B (SEMA4B) interacted with LNM35. Immunoprecipitation experiments confirmed interaction of CLCP1 with SEMA4B, regulation of CLCP1 protein by ubiquitination and proteasome degradation enhanced in the presence of SEMA4B. These results are the first to indicate that CLCP1 plays a role in cell motility, whereas they also showed that at least one of its ligands is SEMA4B and that their interaction mediates proteasome degradation by CLCP1. Although the physiological role of the interaction between CLCP1 and SEMA4B remains to be investigated, this novel gene may become a target of therapy to inhibit metastasis of lung cancers.

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References

  • Bachelder RE, Lipscomb EA, Lin X, Wendt MA, Chadborn NH, Eickholt BJ et al. (2003). Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. Cancer Res 63: 5230–5233.

    CAS  Google Scholar 

  • Burkhardt C, Muller M, Badde A, Garner CC, Gundelfinger ED, Puschel AW . (2005). Semaphorin 4B interacts with the post-synaptic density protein PSD-95/SAP90 and is recruited to synapses through a C-terminal PDZ-binding motif. FEBS Lett 579: 3821–3828.

    Article  CAS  Google Scholar 

  • Castellani V, Falk J, Rougon G . (2004). Semaphorin3A-induced receptor endocytosis during axon guidance responses is mediated by L1 CAM. Mol Cell Neurosci 26: 89–100.

    Article  CAS  Google Scholar 

  • Castro-Rivera E, Ran S, Thorpe P, Minna JD . (2004). Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. Proc Natl Acad Sci USA 101: 11432–11437.

    Article  CAS  Google Scholar 

  • Conrotto P, Valdembri D, Corso S, Serini G, Tamagnone L, Comoglio PM et al. (2005). Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood 105: 4321–4329.

    Article  CAS  Google Scholar 

  • Fournier AE, Nakamura F, Kawamoto S, Goshima Y, Kalb RG, Strittmatter SM . (2000). Semaphorin3A enhances endocytosis at sites of receptor-F-actin colocalization during growth cone collapse. J Cell Biol 149: 411–422.

    Article  CAS  Google Scholar 

  • Friedl P, Wolf K . (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3: 362–374.

    Article  CAS  Google Scholar 

  • Herold C, Elhabazi A, Bismuth G, Bensussan A, Boumsell L . (1996). CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion. J Immunol 157: 5262–5268.

    CAS  PubMed  Google Scholar 

  • Inagaki S, Ohoka Y, Sugimoto H, Fujioka S, Amazaki M, Kurinami H et al. (2001). Sema4c, a transmembrane semaphorin, interacts with a post-synaptic density protein, PSD-95. J Biol Chem 276: 9174–9181.

    Article  CAS  Google Scholar 

  • Kobuke K, Furukawa Y, Sugai M, Tanigaki K, Ohashi N, Matsumori A et al. (2001). ESDN, a novel neuropilin-like membrane protein cloned from vascular cells with the longest secretory signal sequence among eukaryotes, is up-regulated after vascular injury. J Biol Chem 276: 34105–34114.

    Article  CAS  Google Scholar 

  • Koshikawa K, Osada H, Kozaki K, Konishi H, Masuda A, Tatematsu Y et al. (2002). Significant up-regulation of a novel gene, CLCP1, in a highly metastatic lung cancer subline as well as in lung cancers in vivo. Oncogene 21: 2822–2828.

    Article  CAS  Google Scholar 

  • Kozaki K, Koshikawa K, Tatematsu Y, Miyaishi O, Saito H, Hida T et al. (2001). Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI-H460-LNM35 suggest mimicry of inflammatory cells in metastasis. Oncogene 20: 4228–4234.

    Article  CAS  Google Scholar 

  • Kozaki K, Miyaishi O, Tsukamoto T, Tatematsu Y, Hida T, Takahashi T et al. (2000). Establishment and characterization of a human lung cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation. Cancer Res 60: 2535–2540.

    CAS  PubMed  Google Scholar 

  • Kruger RP, Aurandt J, Guan KL . (2005). Semaphorins command cells to move. Nat Rev Mol Cell Biol 6: 789–800.

    Article  CAS  Google Scholar 

  • Oinuma I, Ishikawa Y, Katoh H, Negishi M . (2004). The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science 305: 862–865.

    Article  CAS  Google Scholar 

  • Osada H, Tatematsu Y, Saito H, Yatabe Y, Mitsudomi T, Takahashi T . (2004). Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients. Int J Cancer 112: 26–32.

    Article  CAS  Google Scholar 

  • Tse C, Xiang RH, Bracht T, Naylor SL . (2002). Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res 62: 542–546.

    CAS  PubMed  Google Scholar 

  • Xiang R, Davalos AR, Hensel CH, Zhou XJ, Tse C, Naylor SL . (2002). Semaphorin 3F gene from human 3p21.3 suppresses tumor formation in nude mice. Cancer Res 62: 2637–2643.

    CAS  PubMed  Google Scholar 

  • Yanagisawa K, Uchida K, Nagatake M, Masuda A, Sugiyama M, Saito T et al. (2000). Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers. Oncogene 19: 2305–2311.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Grant-in-Aid for Scientific Research (B) and (C) from the Japan Society for the Promotion of Science, and a Grant-in-Aid for the Second Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan. We thank Kazusa DNA Research Institute for the SEMA4B cDNA clone, KIAA1745.

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Authors and Affiliations

  1. Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan

    H Nagai, H Matsubara & T Takahashi

  2. Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan

    H Nagai, N Sugito, Y Tatematsu, Y Sekido, T Takahashi & H Osada

  3. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    H Nagai, H Matsubara, M Nagino & Y Nimura

  4. Department of Pulmonary Medicine, Aichi Cancer Center Hospital, Nagoya, Japan

    T Hida

Authors
  1. H Nagai
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  2. N Sugito
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  4. Y Tatematsu
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  5. T Hida
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  9. T Takahashi
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  10. H Osada
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Corresponding author

Correspondence to H Osada.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Nagai, H., Sugito, N., Matsubara, H. et al. CLCP1 interacts with semaphorin 4B and regulates motility of lung cancer cells. Oncogene 26, 4025–4031 (2007). https://doi.org/10.1038/sj.onc.1210183

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  • DOI: https://doi.org/10.1038/sj.onc.1210183

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