Targeting protein-trafficking pathways alters melanoma treatment sensitivity
Open accessAbstract
Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis -diaminedichloroplatinum II (cDDP, cis -platin), carboplatin, dacarbazine, or temozolomide together with velaparib, an inhibitor of poly (ADP ribose) polymerase 1, is increased by up to 10-fold by targeting genes that regulate both protein trafficking and the formation of melanosomes, intracellular organelles unique to melanocytes and melanoma cells. Melanoma cells depleted of either of the protein-trafficking regulators vacuolar protein sorting 33A protein (VPS33A) or cappuccino protein (CNO) have increased nuclear localization of cDDP, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. Depleted cells also exhibit a decreased proportion of intracellular, mature melanosomes compared with undepleted cells. Modulation of protein trafficking via cell-surface signaling by binding the melanocortin 1 receptor with the antagonist agouti-signaling protein decreased the proportion of mature melanosomes formed and increased cDDP sensitivity, whereas receptor binding with the agonist melanocyte-stimulating hormone resulted in an increased proportion of mature melanosomes formed and in decreased sensitivity (i.e., increased resistance ) to cDDP. Mutation of the protein-trafficking gene Hps6 , known to impair the formation of mature melanosomes, also increased cDDP sensitivity. Together, these results indicate that targeting protein-trafficking molecules markedly increases melanoma treatment sensitivity and influences the degree of melanosomes available for sequestration of therapeutic agents.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Targeting protein-trafficking pathways alters the sensitivity of melanoma cells to chemotherapy.
“recent studies indicate that targeting protein-trafficking pathways altered the sensitivity of melanoma cells to chemotherapy [34].”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720 · see citing works
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., Lebbe, C., Baurain, J.-F., Testori, A., Grob, J.-J., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104621 · Cited by 4,496 · see citing works
Inhibition of transcription by platinum antitumor compounds
Todd, R. C., & Lippard, S. J. (2009) · Metallomics · doi:10.1039/b907567d · Cited by 539 · see citing works
An integrated approach to uncover drivers of cancer
Akavia, U. D., Litvin, O., Kim, J., Sanchez-Garcia, F., Kotliar, D., Causton, H. C., Pochanard, P., Mozes, E., Garraway, L. A., & Pe'er, D. (2010) · Cell · doi:10.1016/j.cell.2010.11.013 · Cited by 484 · see citing works
Disorders of Lysosome-Related Organelle Biogenesis: Clinical and Molecular Genetics
Huizing, M., Helip‐Wooley, A., Westbroek, W., Gunay‐Aygun, M., & Gahl, W. A. (2008) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164303 · Cited by 413 · see citing works
Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function
Wei, M. L. (2006) · Pigment Cell Research · doi:10.1111/j.1600-0749.2005.00289.x · Cited by 357 · see citing works
Self-citationSuzuki, I., Cone, R. D., Im, S., Nordlund, J. J., & ABDEL‐MALEK, Z. A. (1996) · Endocrinology · doi:10.1210/endo.137.5.8612494 · Cited by 332 · see citing works
BLOC-1 Interacts with BLOC-2 and the AP-3 Complex to Facilitate Protein Trafficking on Endosomes
Pietro, S. M. D., Falcón‐Pérez, J. M., Tenza, D., Setty, S. R. G., Marks, M. S., Raposo, G., & Dell’Angelica, E. C. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-05-0379 · Cited by 232 · see citing works
Setty, S. R. G., Tenza, D., Truschel, S. T., Chou, E., Sviderskaya, E. V., Theos, A. C., Lamoreux, M. L., Pietro, S. M. D., Starcevic, M., Bennett, D. C., et al. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-12-1066 · Cited by 231 · see citing works
Self-citationSlominski, A. T., Zbytek, B., & Slominski, R. M. (2008) · International Journal of Cancer · doi:10.1002/ijc.24005 · Cited by 203 · see citing works
Chen, K. G., Valencia, J. C., Lai, B. C. H., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600213103 · Cited by 189 · see citing works
p16Ink4a in Melanocyte Senescence and Differentiation
Sviderskaya, E. V. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.6.446 · Cited by 177 · see citing works
Self-citationChen, K. G., Valencia, J. C., Gillet, J., Hearing, V. J., & Gottesman, M. M. (2009) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2009.00630.x · Cited by 163 · see citing works
Rébillard, A., Tekpli, X., Meurette, O., Sergent, O., Moigne-Muller, G. L., Vernhet, L., Gorria, M., Chevanne, M., Christmann, M., Kaina, B., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0353 · Cited by 156 · see citing works
Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy
Brożyna, A. A., VanMiddlesworth, L., & Slominski, A. T. (2008) · International Journal of Cancer · doi:10.1002/ijc.23664 · Cited by 137 · see citing works
Suzuki, T., Oiso, N., Gautam, R., Novak, E. K., Panthier, J., Suprabha, P. G., Vida, T. A., Swank, R. T., & Spritz, R. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0237292100 · Cited by 125 · see citing works
Lopes, V. S., Wasmeier, C., Seabra, M. C., & Futter, C. E. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-03-0268 · Cited by 103 · see citing works
Misaki, R., Morimatsu, M., Uemura, T., Waguri, S., Miyoshi, E., Taniguchi, N., Matsuda, M., & Taguchi, T. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200911143 · Cited by 99 · see citing works
Modulation of murine melanocyte function in vitro by agouti signal protein
Sakai, C., Ollmann, M. M., Kobayashi, T., ABDEL‐MALEK, Z. A., Müller, J., Vieira, W. D., Imokawa, G., Barsh, G. S., & Hearing, V. J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3544 · Cited by 97 · see citing works
Influence of Melanosome Dynamics on Melanoma Drug Sensitivity
Chen, K. G., Leapman, R. D., Zhang, G., Lai, B. C. H., Valencia, J. C., CARDARELLI, C. O., Vieira, W. D., Hearing, V. J., & Gottesman, M. M. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djp259 · Cited by 91 · see citing works
Structures of the Agouti Signaling Protein
McNulty, J. C., Jackson, P. J., Thompson, D. A., Chai, B., Gantz, I., Barsh, G. S., Dawson, P. E., & Millhauser, G. L. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.12.030 · Cited by 90 · see citing works
Self-citationGautam, R., Chintala, S., Li, W., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311311200 · Cited by 88 · see citing works
Signaling From the Golgi: Mechanisms and Models for Golgi Phosphoprotein 3–Mediated Oncogenesis
Scott, K. L., & Chin, L. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1695 · Cited by 86 · see citing works
Pape, E. L., Passeron, T., Giubellino, A., Valencia, J. C., Wolber, R., & Hearing, V. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806753106 · Cited by 85 · see citing works
Nguyen, T. N., Kermani, M. J., Fluhr, J. W., Wei, M. L., Novak, E. K., Peters, L. L., & Swank, R. T. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.19535.x · Cited by 77 · see citing works
Self-citationTruschel, S. T., Simoes, S., Setty, S. R. G., Harper, D. C., Tenza, D., Thomas, P. C., Herman, K. E., Sackett, S. D., Cowan, D. C., Theos, A. C., et al. (2009) · Traffic · doi:10.1111/j.1600-0854.2009.00955.x · Cited by 45 · see citing works
Maresca, V., Flori, E., Bellei, B., Aspite, N., Kovacs, D., & Picardo, M. (2010) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2010.00673.x · Cited by 41 · see citing works
Deregulation of Rab5 and Rab4 proteins in p85R274A-expressing cells alters PDGFR trafficking
Chamberlain, M. D., Oberg, J. C., Furber, L. A., Poland, S. F., Hawrysh, A. D., Knafelc, S. M., McBride, H. M., & Anderson, D. H. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.05.025 · Cited by 41 · see citing works
Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes
Xie, T., Nguyen, T. N., Hupe, M., & Wei, M. L. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-0506 · Cited by 40 · see citing works
Self-citationInvolvement of Vps33a in the Fusion of Uroplakin‐Degrading Multivesicular Bodies with Lysosomes
Guo, X., Tu, L., Gumper, I., Plesken, H., Novak, E. K., Chintala, S., Swank, R. T., Pastores, G. M., Torres, P., Izumi, T., et al. (2009) · Traffic · doi:10.1111/j.1600-0854.2009.00950.x · Cited by 39 · see citing works
Characterization of Melanosomes in Murine Hermansky–Pudlak Syndrome: Mechanisms of Hypopigmentation
Nguyen, T. N., & Wei, M. L. (2004) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2004.22117.x · Cited by 35 · see citing works
Self-citationPatel, M. P., Fabersunne, C. C., Yang, Y., Kaelin, C. B., Barsh, G. S., & Millhauser, G. L. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.08.054 · Cited by 32 · see citing works
Self-citationThe BLOC Interactomes Form a Network in Endosomal Transport
Li, W., Feng, Y., Hao, C., Guo, X., Cui, Y., He, M., & He, X. (2007) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/s1673-8527(07)60076-9 · Cited by 31 · see citing works
Ferguson, B. E., & Oh, D. H. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1457 · Cited by 30 · see citing works
Self-citationSviderskaya, E. V., Easty, D. J., Lawrence, M. A., et al. (2009) · The FASEB Journal · doi:10.1096/fj.08-123596 · Cited by 29 · see citing works
Self-citationDistribution and features of melanocytes during inner ear development in pigmented and albino rats
Peters, T. A., Kuijpers, W., Tonnaer, E. L. G. M., van Muijen, G. N. P., & Jap, P. H. K. (1995) · Hearing Research · doi:10.1016/0378-5955(95)00043-4 · Cited by 24 · see citing works
Oh, D. H., & Yeh, K. (2005) · DNA repair · doi:10.1016/j.dnarep.2005.06.004 · Cited by 19 · see citing works
Self-citationKedlaya, R., Kandala, G., Liu, T. F., Maddodi, N., Devi, S., & Setaluri, V. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2011.01.021 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner
Li, Z., Musich, P. R., Cartwright, B. M., Wang, H., & Zou, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068297 · Cited by 26 · see citing works
“sensitivity of cancer cells to chemotherapy agents [34].”
Background
- Authors
- Huang, Z.-M., Chinen, M., Chang, P. J., Xie, T., Zhong, L., Demetriou, S., Patel, M. P., Scherzer, R., Sviderskaya, E. V., Bennett, D. C., Millhauser, G. L., Oh, D. H., Cleaver, J. E., & Wei, M. L.
- Affiliations
- Department of Dermatology, University of California, San Francisco, CA 94115;
- San Francisco VA Medical Center (US)
- University of California, Santa Cruz (US)
- University of London (GB)
- University of California, San Francisco (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-12-27
- Volume
- 109
- Issue
- 2
- Pages
- 553-558
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3258646
- OpenAlex
- W2046159793
- Cited by
- 20
- References
- 38
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 3
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- Melanoma Research Alliance
- Wellcome Trust (078327)
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064265, DK064265)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melanoma, protein trafficking, melanosomes, cisplatin sensitivity, chemoresistance, VPS33A, MC1R, ASIP, melanocyte-stimulating hormone, DNA damage, apoptosis
- MeSH terms
- Temozolomide, Amino Acid Sequence, Antineoplastic Agents, Cisplatin, Dacarbazine, DNA Repair, Humans, Melanoma, Microscopy, Electron, Microscopy, Fluorescence, Molecular Sequence Data, Mutation, Immunoblotting, Down-Regulation, Up-Regulation, Carboplatin, Drug Resistance, Neoplasm, Melanosomes, Protein Transport, Vesicular Transport Proteins, RNA Interference, Receptor, Melanocortin, Type 1, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
