VCP (p97) Regulates NFKB Signaling Pathway, Which Is Important for Metastasis of Osteosarcoma Cell Line
Open accessAbstract
In order to identify genes associated with metastasis, suppression subtractive hybridization (SSH) was performed using murine osteosarcoma cell line Dunn and its subline with higher metastatic potential, LM8. SSH revealed expression of the gene encoding valosin‐containing protein (VCP; also known as p97) to be constitutively activated in LM8 cells, but it declined in Dunn cells when the cells became confluent. Because VCP is known to be involved in the ubiquitination process of Inhibitor‐αBα (IαBα), an inhibitor of nuclear factor‐αB (NFαB), whether VCP influences NFαB activation or not was examined by using VCP‐transfected Dunn cells (Dunn/VCPs). When stimulated with tumor necrosis factor‐α (TNFα), Dunn/VCPs showed constantly activated NFαB, although in the original Dunn cells and control vector transfectant (Dunn/Dunn‐c) NFαB activation ceased when the cells became confluent. Western immunoblot analysis showed an increase of phosphorylated IαBα (p‐IKBα) in the cytoplasm of confluent Dunn/Dunn‐c cells compared to that of Dunn/VCPs. Therefore, decrease of p‐IKBα degrading activity might be responsible for the decrease in NFKB activation. In vitro apoptosis assay demonstrated increased apoptosis rates of Dunn/Dunn‐c cells after TNFα stimulation compared to those of Dunn/VCPs and LM8 cells. In vivo metastasis assay showed increased incidences of metastatic events in Dunn/VCP‐1 inoculated male C3H mice compared to those in Dunn/Dunn‐c inoculated mice. These findings suggested that VCP expression plays an important role in the metastatic process. Anti‐apoptotic potential in these cells owing to constant NFKB activation via efficient cytoplasmic p‐IKBα degrading activity may explain the increased metastatic potential of these cells.
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Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311 · see citing works
Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii
Voth, D. E., & Heinzen, R. A. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.00901.x · Cited by 11,773 · see citing works
Function and Activation of NF-kappaB in the Immune System
Baeuerle, P. A., & Henkel, T. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.001041 · Cited by 4,745 · see citing works
An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
Beg, A. A., & Baltimore, D. (1996) · Science · doi:10.1126/science.274.5288.782 · Cited by 3,047 · see citing works
Diatchenko, L. B., Lau, Y. C., Campbell, A. P., Chenchik, A. A., Moqadam, F., Huang, B. C. B., Lukyanov, S., Lukyanov, K. A., Gurskaya, N. G., Sverdlov, E. D., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.6025 · Cited by 3,009 · see citing works
Wang, C.-Y., Mayo, M., Korneluk, R., Goeddel, D., & Baldwin, A. (1998) · Science · doi:10.1126/science.281.5383.1680 · Cited by 2,950 · see citing works
Suppression of TNF-α-Induced Apoptosis by NF-κB
Antwerp, D. J. V., Martin, S. J., Kafri, T., Green, D. R., & Verma, I. M. (1996) · Science · doi:10.1126/science.274.5288.787 · Cited by 2,581 · see citing works
IκB: a Specific Inhibitor of the NF-κB Transcription Factor
Baeuerle, P. A., & Baltimore, D. (1988) · Science · doi:10.1126/science.3140380 · Cited by 2,154 · see citing works
The pathogenesis of cancer metastasis
Poste, G. H., & Fidler, I. J. (1980) · Nature · doi:10.1038/283139a0 · Cited by 1,739 · see citing works
Genomic analysis of metastasis reveals an essential role for RhoC
Clark, E. A., Golub, T. R., Lander, E. S., & Hynes, R. O. (2000) · Nature · doi:10.1038/35020106 · Cited by 1,444 · see citing works
Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB
Baldwin, A. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11991 · Cited by 1,427 · see citing works
Traenckner, E. B.-M., Pahl, H. L., Henkel, T., Schmidt, K. N., Wilk, S., & Baeuerle, P. A. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07287.x · Cited by 1,014 · see citing works
Carthew, R. W., Chodosh, L. A., & Sharp, P. A. (1985) · Cell · doi:10.1016/0092-8674(85)90174-6 · Cited by 763 · see citing works
Bargou, R. C., Emmerich, F., Krappmann, D., Bommert, K., Mapara, M. Y., Arnold, W., Royer, H., Grinstein, E., Greiner, A., Scheidereit, C., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119849 · Cited by 757 · see citing works
Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer.
Sovak, M. A., Bellas, R. E., Kim, D. W., Zanieski, G., Rogers, A. E., Traish, A. M., & Sonenshein, G. E. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119848 · Cited by 720 · see citing works
Beg, A. A., Ruben, S. M., Scheinman, R. I., Haskill, S., Rosen, C. A., & Baldwin, A. S. (1992) · Genes & Development · doi:10.17615/1ytj-h979 · Cited by 718 · see citing works
Mapping of the Inducible IκB Phosphorylation Sites That Signal Its Ubiquitination and Degradation†
Didonato, J., Mercurio, F., Rosette, C., Wu-Li, J., Suyang, H., Ghosh, S., & Karin, M. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1295 · Cited by 707 · see citing works
Wang, C.-Y., D, D. C. G., Mayo, M. W., & Baldwin, A. S. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.5923 · Cited by 586 · see citing works
Lee, K. A. W., Bindereif, A., & Green, M. R. (1988) · Gene Analysis Techniques · doi:10.1016/0735-0651(88)90023-4 · Cited by 481 · see citing works
Synergistic Roles for Pim-1 and c-Myc in STAT3-Mediated Cell Cycle Progression and Antiapoptosis
Shirogane, T., Fukada, T., Müller, J. M. M., Shima, D. T., Hibi, M., & Hirano, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80145-4 · Cited by 427 · see citing works
Cameron, M. D., Schmidt, E. E., Kerkvliet, N. I., Nadkarni, K. V., Morris, V. L., Groom, A. C., Chambers, A. F., & MacDonald, I. C. (2000) · PubMed · Cited by 400 · see citing works
Membrane fusion and the cell cycle: Cdc48p participates in the fusion of ER membranes
Latterich, M., Fröhlich, K.-U., & Schekman, R. (1995) · Cell · doi:10.1016/0092-8674(95)90268-6 · Cited by 388 · see citing works
The transcription factor NF-κB: control of oncogenesis and cancer therapy resistance
Mayo, M. W., & Baldwin, A. S. (2000) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(00)00002-0 · Cited by 323 · see citing works
Dai, R., Chen, E., Longo, D. L., Gorbea, C. M., & Li, C.-C. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3562 · Cited by 315 · see citing works
Metastasis-Suppressor Genes: a Review and Perspective on an Emerging Field
Yoshida, B. A. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.21.1717 · Cited by 270 · see citing works
Steps in tumor metastasis: new concepts from intravital videomicroscopy
Chambers, A. F., MacDonald, I. C., Schmidt, E. E., Koop, S., Morris, V. L., Khokha, R., & Groom, A. C. (1995) · Cancer and Metastasis Reviews · doi:10.1007/bf00690599 · Cited by 265 · see citing works
Rabouille, C., Kondo, H., Newman, R., Hui, N., Freemont, P. S., & Warren, G. (1998) · Cell · doi:10.1016/s0092-8674(00)81128-9 · Cited by 256 · see citing works
Epstein–Barr Virus and a Cellular Signaling Pathway in Lymphomas from Immunosuppressed Patients
Liebowitz, D. N. (1998) · New England Journal of Medicine · doi:10.1056/nejm199805143382003 · Cited by 232 · see citing works
Cell Contact-Dependent Signaling
Fagotto, F., & Gumbiner, B. M. (1996) · Developmental Biology · doi:10.1006/dbio.1996.0318 · Cited by 223 · see citing works
Role of I Bα Ubiquitination in Signal-induced Activation of NF- B in Vivo
Roff, M. A., Thompson, J., Rodríguez, M. S., Jacqué, J.-M., Baleux, F., Arenzana‐Seisdedos, F., & Hay, R. T. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.13.7844 · Cited by 215 · see citing works
Kirillova, I., Chaisson, M. L., & Fausto, N. (1999) · PubMed · Cited by 143 · see citing works
Bacci, G., Ferrari, S., Delépine, N., Bertoni, F., Picci, P., Mercuri, M., Bacchini, P., del Prever, A. B., Tienghi, A., Comandone, A., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.2.658 · Cited by 141 · see citing works
Morris, V. L., Koop, S., MacDonald, I. C., Schmidt, E. E., Grattan, M., Percy, D. H., Chambers, A. F., & Groom, A. C. (1994) · Clinical & Experimental Metastasis · doi:10.1007/bf01755879 · Cited by 133 · see citing works
Nicolson, G. L. (1993) · Cancer and Metastasis Reviews · doi:10.1007/bf00665961 · Cited by 130 · see citing works
Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate.
Melchior, S. W., Corey, E., Ellis, W. J., et al. (1997) · PubMed · Cited by 128 · see citing works
Koop, S., Schmidt, E. E., MacDonald, I. C., Morris, V. L., Khokha, R., Grattan, M., Leone, J., Chambers, A. F., & Groom, A. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.11080 · Cited by 111 · see citing works
Ganchi, P. A., Sun, S., Greene, W. C., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.12.7826-7835.1993 · Cited by 107 · see citing works
Molecular Basis of Tumor Progression: Mechanisms of Organ‐Specific Tumor Metastasis
Yeatman, T. J., & Nicolson, G. L. (1993) · Seminars in Surgical Oncology · doi:10.1002/j.1098-2388.1993.tb00018.x · Cited by 89 · see citing works
What Defines a Useful Marker of Metastasis in Human Cancer?
Welch, D. R., & Rinker-Schaeffer, C. W. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.16.1351 · Cited by 70 · see citing works
Increased invasiveness ofMUCI1 cDNA-transfected human gastric cancer MKN74 cells
Suwa, T., Hinoda, Y., Makiguchi, Y., Takahashi, T., Itoh, F., Adachi, M., Hareyama, M., & Imai, K. (1998) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19980504)76:3 · Cited by 62 · see citing works
Ganchi, P. A., Sun, S. C., Greene, W. C., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.12.7826 · Cited by 61 · see citing works
Search for Genes That Suppress Cancer Metastasis
Fidler, I. J., & Radinsky, R. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.23.1700 · Cited by 53 · see citing works
Müller, J. M. M., Meyer, H. H., Ruhrberg, C., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.15.10154 · Cited by 34 · see citing works
OSTEOSARCOMA: Specific Tumor Management and Results
LaQuaglia, M. P. (1998) · Chest Surgery Clinics of North America · doi:10.1016/s1052-3359(25)00316-3 · Cited by 30 · see citing works
Development of markers of prostate cancer metastasis
Christiano, A. P., Yoshida, B. A., Dubauskas, Z., et al. (2000) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/s1078-1439(00)00070-3 · Cited by 28 · see citing works
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Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
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- Authors
- Asai, T., Tomita, Y., Nakatsuka, S., Hoshida, Y., Myoui, A., Yoshikawa, H., & Aozasa, K.
- Affiliations
- The University of Osaka (JP)
- Corresponding author
- Tomita, Yasuhiko
- Venue
- Japanese Journal of Cancer Research
- Publisher
- Wiley
- Published
- 2002-03
- Volume
- 93
- Issue
- 3
- Pages
- 296-304
- ISSN
- 0910-5050 (ISSN-L)
- PMC
- PMC5926968
- OpenAlex
- W1994246241
- Cited by
- 155
- References
- 46
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2022: 15 · 2021: 6 · 2020: 4 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 17 · 2012: 6
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Japanese Journal of Cancer Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- VCP, osteosarcoma, metastasis, NF-κB signaling, IκBα phosphorylation, ubiquitination, TNF-α, apoptosis, cell confluence
- MeSH terms
- Valosin Containing Protein, Adenosine Triphosphatases, Animals, Bone Neoplasms, Gene Expression Regulation, Humans, Lung Neoplasms, Male, Mice, Inbred C3H, Microscopy, Fluorescence, Plasmids, Osteosarcoma, Transfection, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Blotting, Northern, Signal Transduction, NF-kappa B, Apoptosis, DNA Primers, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, Electrophoretic Mobility Shift Assay, Mice
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