The DOI matches its Crossref record; 47 of the 49 references it cites were found in a registry or an index.
AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer
Open accessPublished version of a preprint
Abstract
The receptor tyrosine kinase AXL is thought to play a role in metastasis; however, the therapeutic efficacy of an AXL-targeting agent remains largely untested in metastatic disease. In this study, we defined AXL as a therapeutic target for metastatic ovarian cancer. AXL is primarily expressed in metastases and advanced-stage human ovarian tumors but not in normal ovarian epithelium. Genetic inhibition of AXL in human metastatic ovarian tumor cells is sufficient to prevent the initiation of metastatic disease in vivo. Mechanistically, inhibition of AXL signaling in animals with metastatic disease results in decreased invasion and matrix metalloproteinase activity. Most importantly, soluble human AXL receptors that imposed a specific blockade of the GAS6/AXL pathway had a profound inhibitory effect on progression of established metastatic ovarian cancer without normal tissue toxicity. These results offer the first genetic validation of GAS6/AXL targeting as an effective strategy for inhibition of metastatic tumor progression in vivo. Furthermore, this study defines the soluble AXL receptor as a therapeutic candidate agent for treatment of metastatic ovarian cancer, for which current therapies are ineffective. Cancer Res; 70(19); 7570–9. ©2010 AACR.
Overview
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
Verification
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?
In the citing paper
“A growing body of literature supports an essential role for AXL in promoting metastasis within many tumor types, including breast (81), ovarian (82), and lung (83).”
From Hypoxic control of metastasis (2016) · cites this paper as [82]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Budagian, V., Bulanova, E., Orinska, Z., Duitman, E. H., Brandt, K., Ludwig, A., Hartmann, D., Lemke, G., Säftig, P., & Bulfone‐Paus, S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9324-9339.2005 · Cited by 84
RetractedNew functions for the matrix metalloproteinases in cancer progression
Egeblad, M., & Werb, Z. (2002) · Nature Reviews Cancer · doi:10.1038/nrc745 · Cited by 6,108
Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
Coussens, L. M., Fingleton, B., & Matrisian, L. M. (2002) · Science · doi:10.1126/science.1067100 · Cited by 2,761
The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory
Kurman, R. J., & Shih, I. (2010) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181cf3d79 · Cited by 1,890
Tumor Self-Seeding by Circulating Cancer Cells
Kim, M.-Y., Oskarsson, T., Acharyya, S., Nguyen, D. X., Zhang, X. H.-F., Norton, L., & Massagué, J. (2009) · Cell · doi:10.1016/j.cell.2009.11.025 · Cited by 1,335
Linger, R. M. A., Keating, A. K., Earp, H. S., & Graham, D. K. (2008) · Advances in cancer research · doi:10.1016/s0065-230x(08)00002-x · Cited by 750
O’Bryan, J. P., Frye, R. A., Cogswell, P. C., Neubauer, A., Kitch, B., Prokop, C. A., Espinosa, R., Beau, M. M. L., Earp, H. S., & Liu, E. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.10.5016 · Cited by 746
Homeostatic Regulation of the Immune System by Receptor Tyrosine Kinases of the Tyro 3 Family
Lu, Q., & Lemke, G. (2001) · Science · doi:10.1126/science.1061663 · Cited by 699
Gjerdrum, C., Tiron, C., Høiby, T., Stefansson, I., Haugen, H., Sandal, T., Collett, K., Li, S., McCormack, E., Gjertsen, B. T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909333107 · Cited by 594
Holland, S. J., Pan, A., Franci, C., Hu, Y., Chang, B. Y., Li, W., Duan, M., Torneros, A., Yu, J., Heckrodt, T. J., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2997 · Cited by 567
Illuminating the metastatic process
Sahai, E. A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2229 · Cited by 566
Targeting phosphoinositide 3-kinase—Moving towards therapy
Marone, R., Cmiljanović, V., Giese, B., & Wymann, M. P. (2007) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.10.003 · Cited by 560
Ovarian Cancer Metastasis: Integrating insights from disparate model organisms
Naora, H., & Montell, D. J. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1611 · Cited by 547
Nagata, K., Ohashi, K., Nakano, T., Arita, H., Zong, C., Hanafusa, H., & Mizuno, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.30022 · Cited by 541
Mechanisms of transcoelomic metastasis in ovarian cancer
Tan, D. S. P., Agarwal, R., & Kaye, S. B. (2006) · The Lancet Oncology · doi:10.1016/s1470-2045(06)70939-1 · Cited by 529
Tyro-3 family receptors are essential regulators of mammalian spermatogenesis
Lu, Q., Gore, M., Zhang, Q., Camenisch, T., Boast, S., Casagranda, F., Lai, C., Skinner, M. K., Klein, R., Matsushima, G. K., et al. (1999) · Nature · doi:10.1038/19554 · Cited by 514
Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis
Angelillo-Scherrer, A., de Frutos, P. G., Aparicio, C., Melis, E., Savi, P., Lupu, F., Arnout, J., Dewerchin, M., Hoylaerts, M. F., Herbert, J.-M., et al. (2001) · Nature Medicine · doi:10.1038/84667 · Cited by 441
Yuan, Z. Q., Sun, M., Feldman, R. I., Wang, G., Xiaoling, M., Jiang, C. C., Coppola, D., Nicosia, S. V., & Cheng, J. Q. (2000) · Oncogene · doi:10.1038/sj.onc.1203598 · Cited by 385
Expression of Angiogenesis-Related Genes and Progression of Human Ovarian Carcinomas in Nude Mice
Yoneda, J., Kuniyasu, H., Price, J. E., Bucana, C. D., Fidler, I. J., & Crispens, M. A. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.6.447 · Cited by 375
Precursor lesions of ovarian epithelial malignancy
Feeley, K. M., & Wells, M. L. (2001) · Histopathology · doi:10.1046/j.1365-2559.2001.01042.x · Cited by 351
Bonome, T., Lee, J.-Y., Park, D.-C., Radonovich, M., Pise-Masison, C. A., Brady, J. N., Gardner, G. J., Hao, K., Wong, W. H., Barrett, J. C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2240 · Cited by 315
Li, Y., Ye, X., Tan, C., Hongo, J. A., Zha, J., Liu, J., Kallop, D. Y., Ludlam, M. J. C., & Pei, L. (2009) · Oncogene · doi:10.1038/onc.2009.212 · Cited by 294
Expression of Axl in Lung Adenocarcinoma and Correlation with Tumor Progression
Shinh, Y.-S., Lai, C.-Y., Kao, Y.-R., Shiah, S., Chu, Y., Lee, H., & Wu, C. (2005) · Neoplasia · doi:10.1593/neo.05640 · Cited by 274
Kuo, C. J., Farnebo, F. A., Yu, E. Y., Christofferson, R. H. B., Swearingen, R. A., Carter, R., von Recum, H. A., Yuan, J., Kamihara, J., Flynn, E. A., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081615298 · Cited by 268
Self-citationTwist mediates suppression of inflammation by type I IFNs and Axl
Sharif, M. N., Šošić, D., Rothlin, C. V., Kelly, E., Lemke, G., Olson, E. N., & Ivashkiv, L. B. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051725 · Cited by 251
Vajkoczy, P., Knyazev, P. G., Kunkel, A., Capelle, H., Behrndt, S., von Tengg‐Kobligk, H., Kiessling, F. M., Eichelsbacher, U., Essig, M., Read, T., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510923103 · Cited by 239
Hong, C., Lay, J., Huang, J.-S., Cheng, A., Tang, J., Lin, M., Lai, G., & Chuang, S. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.04.017 · Cited by 234
O’Bryan, J. P., Frye, R. A., Cogswell, P. C., Neubauer, A., Kitch, B., Prokop, C. A., Espinosa, R., Beau, M. M. L., Earp, H. S., & Liu, E. T. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.10.5016-5031.1991 · Cited by 232
AXL Is a Potential Target for Therapeutic Intervention in Breast Cancer Progression
Zhang, Y., Knyazev, P. G., Cheburkin, Y. V., Sharma, K., Knyazev, Y. P., Őrfi, L., Szabadkai, I., Daub, H., Kéri, G., & Ullrich, A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2661 · Cited by 217
Koorstra, J.-B. M., Karikari, C. A., Feldmann, G., Bisht, S., Rojas, P. L., Offerhaus, G. J. A., Alvarez, H., & Maitra, A. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.7.7923 · Cited by 208
Multiple Roles for the Receptor Tyrosine Kinase Axl in Tumor Formation
Holland, S. J., Powell, M. J., Franci, C., Chan, E. W., Friera, A. M., Atchison, R. E., McLaughlin, J. R., Swift, S. E., Pali, E. S., Yam, G. C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0993 · Cited by 204
GAS6 Induces Axl-mediated Chemotaxis of Vascular Smooth Muscle Cells
Fridell, Y.-W. C., Villa, J., Attar, E. C., & Liu, E. T. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.12.7123 · Cited by 195
Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-κB and Brg-1
Tai, K.-Y., Shieh, Y.-S., Lee, C.-S., Shiah, S., & Wu, C.-W. (2008) · Oncogene · doi:10.1038/onc.2008.57 · Cited by 170
Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases
Caraux, A., Lu, Q., Fernandez, N. C., Riou, S., Santo, J. P. D., Raulet, D. H., Lemke, G., & Roth, C. (2006) · Nature Immunology · doi:10.1038/ni1353 · Cited by 157
Mills, G. B., Lu, Y., Fang, X., Wang, H., Eder, A., Mao, M., Swaby, R., Cheng, K. W., Stokoe, D., Siminovitch, K., et al. (2001) · Seminars in Oncology · doi:10.1016/s0093-7754(01)90290-8 · Cited by 133
Liu, A. X., Testa, J. R., Hamilton, T. C., Jove, R., Nicosia, S. V., & Cheng, J. Q. (1998) · PubMed · Cited by 130
Lay, J., Hong, C., Huang, J.-S., Yang, Y.-Y., Pao, C.-Y., Liu, C.-H., Lai, Y.-P., Lai, G., Cheng, A., Su, I., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3191 · Cited by 114
Role of Gas6 in erythropoiesis and anemia in mice
Angelillo‐Scherrer, A., Burnier, L., Lambrechts, D., Fish, R. J., Tjwa, M., Plaisance, S., Sugamele, R., DeMol, M., Martínez-Soria, E., Maxwell, P. H., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci30375 · Cited by 105
Kuhnert, F., Tam, B. Y. Y., Sennino, B., Gray, J. T., Yuan, J., Jocson, A., Nayak, N. R., Mulligan, R. C., McDonald, D. M., & Kuo, C. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803194105 · Cited by 97
Self-citationCrystal Structure of a C-terminal Fragment of Growth Arrest-specific Protein Gas6
Sasaki, T., Knyazev, P. G., Cheburkin, Y. V., Göhring, W., Tisi, D., Ullrich, A., Timpl, R., & Hohenester, E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207340200 · Cited by 91
Choi, J., Choi, K., Auersperg, N., & Leung, P. C. K. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1785 · Cited by 73
Lancaster, J. M., Dressman, H. K., Clarke, J., Sayer, R. A., Martino, M. A., Cragun, J. M., Henriott, A., Gray, J., Sutphen, R., Elahi, A. H., et al. (2006) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2006.00660.x · Cited by 67
Nielsen‐Preiss, S. M., Allen, M. P., Xu, M., Linseman, D. A., Pawlowski, J. E., Bouchard, R. J., Varnum, B. C., Heidenreich, K. A., & Wierman, M. E. (2007) · Endocrinology · doi:10.1210/en.2007-0039 · Cited by 62
Inflammation: A hidden path to breaking the spell of ovarian cancer
Shan, W., & Liu, J. (2009) · Cell Cycle · doi:10.4161/cc.8.19.9590 · Cited by 60
Guo, R., Qiao, Y., Zhou, Y., Li, L., Shi, H., & Chen, K. (2008) · Pathology International · doi:10.1111/j.1440-1827.2008.02306.x · Cited by 60
Differential effects of NGF and NT-3 on embryonic trigeminal axon growth patterns
Ulupınar, E., Jacquin, M. F., & Erzurumlu, R. S. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000918)425:2 · Cited by 52
New agents for the treatment of ovarian cancer: the next generation
Dupont, J., Aghajanian, C. A., Sabbatini, P. J., & Spriggs, D. R. (2005) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2005.00443.x · Cited by 11
Cited by
Sorted by citations
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340
Self-citationBiomarkers for the early diagnosis of hepatocellular carcinoma
Tsuchiya, N. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i37.10573 · Cited by 571
Zhu, C., Wei, Y., & Wei, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1090-3 · Cited by 507
Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma
Zhou, L., Liu, X.-D., Sun, M., Zhang, X., German, P., Bai, S., Ding, Z., Tannir, N. M., Wood, C. G., Matin, S. F., et al. (2015) · Oncogene · doi:10.1038/onc.2015.343 · Cited by 400
Self-citationAsiedu, M. K., Beauchamp‐Perez, F., Ingle, J. N., Behrens, M. D., Radisky, D. C., & Knutson, K. L. (2013) · Oncogene · doi:10.1038/onc.2013.57 · Cited by 302
Metadata
- Authors
- Rankin, E. B., Fuh, K. C., Taylor, T. E., Krieg, A. J., Musser, M., Yuan, J., Wei, K., Kuo, C. J., Longacre, T. A., & Giaccia, A. J.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Giaccia, Amato J.
- ORCID
- Venue
- Cancer Research
- Published
- 2010-09-29
- Volume
- 70
- Issue
- 19
- Pages
- 7570-7579
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3408227
- OpenAlex
- W2132286757
- Cited by
- 229
- References
- 49
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 16 · 2023: 14 · 2022: 16 · 2021: 18 · 2020: 13 · 2019: 14 · 2018: 18 · 2017: 17 · 2016: 25 · 2015: 20 · 2014: 14 · 2013: 16 · 2012: 6
- FWCI
- 11.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA116685, P01CA067166, T32CA009151, T32CA09151, F32CA124082, CA 67166, R01CA116685, T32CA009302)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK085532, U01DK085527, U01DK085532)
- Topics
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- AXL receptor tyrosine kinase, metastatic ovarian cancer, therapeutic target, tumor invasion, matrix metalloproteinase activity, metastasis suppression
- MeSH terms
- Axl Receptor Tyrosine Kinase, Growth Arrest-Specific Protein 6, Adenoviridae, Animals, Female, Humans, Mice, Nude, Neoplasm Metastasis, Ovarian Neoplasms, Plasmids, Proto-Oncogene Proteins, Signal Transduction, Receptor Protein-Tyrosine Kinases, Xenograft Model Antitumor Assays, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Mice
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
