An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis
Abstract
Aberrant signaling through the Axl receptor tyrosine kinase has been associated with a myriad of human diseases, most notably metastatic cancer, identifying Axl and its ligand Gas6 as important therapeutic targets. Using rational and combinatorial approaches, we engineered an Axl ‘decoy receptor’ that binds Gas6 with high affinity and inhibits its function, offering an alternative approach from drug discovery efforts that directly target Axl. Four mutations within this high affinity Axl variant caused structural alterations in side chains across the Gas6/Axl binding interface, stabilizing a conformational change on Gas6. When reformatted as an Fc-fusion, the engineered decoy receptor bound to Gas6 with femtomolar affinity, an 80-fold improvement compared to the wild-type Axl receptor, allowing effective sequestration of Gas6 and specific abrogation of Axl signaling. Additionally, increased Gas6 binding affinity was critical and correlative with the ability of decoy receptors to potently inhibit metastasis and disease progression in vivo.
- Authors:
-
- Stanford Univ., CA (United States). Dept. of Bioengineering
- Stanford Univ., CA (United States). Stanford University School of Medicine, Dept. of Radiation Oncology
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Stanford Univ., CA (United States). Dept. of Bioengineering; Stanford Univ., CA (United States). Dept. of Chemical Engineering
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1293893
- Grant/Contract Number:
- NIH CA-088480; NIH CA-67166; T32 GM008412-15S1
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Chemical Biology
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 11; Journal ID: ISSN 1552-4450
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Cancer therapy; Cell signalling; Combinatorial libraries; Kinases
Citation Formats
Kariolis, Mihalis S., Miao, Yu Rebecca, Jones, Douglas S., Kapur, Shiven, Mathews, Irimpan I., Giaccia, Amato J., and Cochran, Jennifer R. An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis. United States: N. p., 2014.
Web. doi:10.1038/nchembio.1636.
Kariolis, Mihalis S., Miao, Yu Rebecca, Jones, Douglas S., Kapur, Shiven, Mathews, Irimpan I., Giaccia, Amato J., & Cochran, Jennifer R. An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis. United States. https://doi.org/10.1038/nchembio.1636
Kariolis, Mihalis S., Miao, Yu Rebecca, Jones, Douglas S., Kapur, Shiven, Mathews, Irimpan I., Giaccia, Amato J., and Cochran, Jennifer R. Sun .
"An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis". United States. https://doi.org/10.1038/nchembio.1636. https://www.osti.gov/servlets/purl/1293893.
@article{osti_1293893,
title = {An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis},
author = {Kariolis, Mihalis S. and Miao, Yu Rebecca and Jones, Douglas S. and Kapur, Shiven and Mathews, Irimpan I. and Giaccia, Amato J. and Cochran, Jennifer R.},
abstractNote = {Aberrant signaling through the Axl receptor tyrosine kinase has been associated with a myriad of human diseases, most notably metastatic cancer, identifying Axl and its ligand Gas6 as important therapeutic targets. Using rational and combinatorial approaches, we engineered an Axl ‘decoy receptor’ that binds Gas6 with high affinity and inhibits its function, offering an alternative approach from drug discovery efforts that directly target Axl. Four mutations within this high affinity Axl variant caused structural alterations in side chains across the Gas6/Axl binding interface, stabilizing a conformational change on Gas6. When reformatted as an Fc-fusion, the engineered decoy receptor bound to Gas6 with femtomolar affinity, an 80-fold improvement compared to the wild-type Axl receptor, allowing effective sequestration of Gas6 and specific abrogation of Axl signaling. Additionally, increased Gas6 binding affinity was critical and correlative with the ability of decoy receptors to potently inhibit metastasis and disease progression in vivo.},
doi = {10.1038/nchembio.1636},
journal = {Nature Chemical Biology},
number = 11,
volume = 10,
place = {United States},
year = {Sun Sep 21 00:00:00 EDT 2014},
month = {Sun Sep 21 00:00:00 EDT 2014}
}
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Works referenced in this record:
Immunobiology of the TAM receptors
journal, May 2008
- Lemke, Greg; Rothlin, Carla V.
- Nature Reviews Immunology, Vol. 8, Issue 5
Axl as a potential therapeutic target in cancer: role of Axl in tumor growth, metastasis and angiogenesis
journal, July 2009
- Li, Y.; Ye, X.; Tan, C.
- Oncogene, Vol. 28, Issue 39
Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer
journal, July 2012
- Zhang, Zhenfeng; Lee, Jae Cheol; Lin, Luping
- Nature Genetics, Vol. 44, Issue 8
ABL Regulation by AXL Promotes Cisplatin Resistance in Esophageal Cancer
journal, November 2012
- Hong, Jun; Peng, DunFa; Chen, Zheng
- Cancer Research, Vol. 73, Issue 1
An Epithelial-Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance
journal, October 2012
- Byers, L. A.; Diao, L.; Wang, J.
- Clinical Cancer Research, Vol. 19, Issue 1
Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival
journal, April 2006
- Vajkoczy, P.; Knyazev, P.; Kunkel, A.
- Proceedings of the National Academy of Sciences, Vol. 103, Issue 15
Differential Expression of Axl and Gas6 in Renal Cell Carcinoma Reflecting Tumor Advancement and Survival
journal, June 2009
- Gustafsson, A.; Martuszewska, D.; Johansson, M.
- Clinical Cancer Research, Vol. 15, Issue 14
Axl and prostasin are biomarkers for prognosis of ovarian adenocarcinoma
journal, October 2013
- Chen, Pu-xiang; Li, Qiao-yan; Yang, Zhulin
- Annals of Diagnostic Pathology, Vol. 17, Issue 5
AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer
journal, September 2010
- Rankin, E. B.; Fuh, K. C.; Taylor, T. E.
- Cancer Research, Vol. 70, Issue 19
R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer
journal, February 2010
- Holland, S. J.; Pan, A.; Franci, C.
- Cancer Research, Vol. 70, Issue 4
LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models
journal, December 2012
- Yan, S. Betty; Peek, Victoria L.; Ajamie, Rose
- Investigational New Drugs, Vol. 31, Issue 4
An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies
journal, July 2010
- Ye, X.; Li, Y.; Stawicki, S.
- Oncogene, Vol. 29, Issue 38
Preclinical validation of AXL receptor as a target for antibody-based pancreatic cancer immunotherapy
journal, November 2013
- Leconet, W.; Larbouret, C.; Chardès, T.
- Oncogene, Vol. 33, Issue 47
Targeting Axl With an High-affinity Inhibitory Aptamer
journal, December 2012
- Cerchia, Laura; Esposito, Carla L.; Camorani, Simona
- Molecular Therapy, Vol. 20, Issue 12
The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells
journal, February 2014
- Paolino, Magdalena; Choidas, Axel; Wallner, Stephanie
- Nature, Vol. 507, Issue 7493
A small molecule–kinase interaction map for clinical kinase inhibitors
journal, February 2005
- Fabian, Miles A.; Biggs, William H.; Treiber, Daniel K.
- Nature Biotechnology, Vol. 23, Issue 3
A novel site contributing to growth-arrest-specific gene 6 binding to its receptors as revealed by a human monoclonal antibody
journal, April 2005
- Fisher, Paul W.; Brigham-Burke, Michael; Wu, Sheng-Jiun
- Biochemical Journal, Vol. 387, Issue 3
Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6
journal, February 1995
- Varnum, Brian C.; Young, Cynthia; Elliott, Gary
- Nature, Vol. 373, Issue 6515
Beyond antibodies: using biological principles to guide the development of next-generation protein therapeutics
journal, December 2013
- Kariolis, Mihalis S.; Kapur, Shiven; Cochran, Jennifer R.
- Current Opinion in Biotechnology, Vol. 24, Issue 6
Cytokine traps: multi-component, high-affinity blockers of cytokine action
journal, December 2002
- Economides, Aris N.; Carpenter, Laura Rocco; Rudge, John S.
- Nature Medicine, Vol. 9, Issue 1
A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity
journal, December 1991
- Peppel, K.
- Journal of Experimental Medicine, Vol. 174, Issue 6
VEGF-Trap: A VEGF blocker with potent antitumor effects
journal, August 2002
- Holash, J.; Davis, S.; Papadopoulos, N.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 17
Structural basis for Gas6–Axl signalling
journal, December 2005
- Sasaki, Takako; Knyazev, Pjotr G.; Clout, Naomi J.
- The EMBO Journal, Vol. 25, Issue 1
Kinetic Exclusion Assay Technology: Characterization of Molecular Interactions
journal, December 2004
- Darling, Ryan J.; Brault, Pierre-Alexandre
- ASSAY and Drug Development Technologies, Vol. 2, Issue 6
Gas6 and protein S: Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily
journal, October 2006
- Hafizi, Sassan; Dahlbäck, Björn
- FEBS Journal, Vol. 273, Issue 23
The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.
journal, August 1993
- Manfioletti, G.; Brancolini, C.; Avanzi, G.
- Molecular and Cellular Biology, Vol. 13, Issue 8
Crystal Structure of a C-terminal Fragment of Growth Arrest-specific Protein Gas6: RECEPTOR TYROSINE KINASE ACTIVATION BY LAMININ G-LIKE DOMAINS
journal, September 2002
- Sasaki, Takako; Knyazev, Pjotr G.; Cheburkin, Yuri
- Journal of Biological Chemistry, Vol. 277, Issue 46
Helix capping propensities in peptides parallel those in proteins
journal, December 1993
- Chakrabartty, A.; Doig, A. J.; Baldwin, R. L.
- Proceedings of the National Academy of Sciences, Vol. 90, Issue 23
Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’
journal, March 2012
- Levin, Aron M.; Bates, Darren L.; Ring, Aaron M.
- Nature, Vol. 484, Issue 7395
Rational design and engineering of therapeutic proteins
journal, March 2003
- Marshall, Shannon A.; Lazar, Greg A.; Chirino, Arthur J.
- Drug Discovery Today, Vol. 8, Issue 5
Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival
journal, December 2009
- Gjerdrum, C.; Tiron, C.; Hoiby, T.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 3
Tumor metastasis: moving new biological insights into the clinic
journal, November 2013
- Wan, Liling; Pantel, Klaus; Kang, Yibin
- Nature Medicine, Vol. 19, Issue 11
Tyro-3 family receptors are essential regulators of mammalian spermatogenesis
journal, April 1999
- Lu, Qingxian; Gore, Martin; Zhang, Qing
- Nature, Vol. 398, Issue 6729
Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis
journal, February 2001
- Angelillo-Scherrer, Anne; de Frutos, Pablo Garcia; Aparicio, Cristina
- Nature Medicine, Vol. 7, Issue 2
Yeast surface display for screening combinatorial polypeptide libraries
journal, June 1997
- Boder, Eric T.; Wittrup, K. Dane
- Nature Biotechnology, Vol. 15, Issue 6
Isolating and engineering human antibodies using yeast surface display
journal, July 2006
- Chao, Ginger; Lau, Wai L.; Hackel, Benjamin J.
- Nature Protocols, Vol. 1, Issue 2
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
Molecular replacement with MOLREP
journal, December 2009
- Vagin, Alexei; Teplyakov, Alexei
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997
- Murshudov, G. N.; Vagin, A. A.; Dodson, E. J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3
Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007
- Krissinel, Evgeny; Henrick, Kim
- Journal of Molecular Biology, Vol. 372, Issue 3
Flexibility analysis of enzyme active sites by crystallographic temperature factors
journal, February 2003
- Yuan, Zheng; Zhao, Ju; Wang, Zhi-Xin
- Protein Engineering, Design and Selection, Vol. 16, Issue 2
Works referencing / citing this record:
Engineered ligand-based VEGFR antagonists with increased receptor binding affinity more effectively inhibit angiogenesis: Kapur et al.
journal, February 2017
- Kapur, Shiven; Silverman, Adam P.; Ye, Anne Z.
- Bioengineering & Translational Medicine, Vol. 2, Issue 1
Applications of Yeast Surface Display for Protein Engineering
book, January 2015
- Cherf, Gerald M.; Cochran, Jennifer R.
- Methods in Molecular Biology
Axl and Mer Receptor Tyrosine Kinases: Distinct and Nonoverlapping Roles in Inflammation and Cancer?
book, January 2016
- Dransfield, Ian; Farnworth, Sarah
- Apoptosis in Cancer Pathogenesis and Anti-cancer Therapy
Apoptotic cell clearance in the tumor microenvironment: a potential cancer therapeutic target
journal, June 2019
- Shin, Seong-Ah; Moon, Sun Young; Park, Daeho
- Archives of Pharmacal Research, Vol. 42, Issue 8
Molecular insights of Gas6/TAM in cancer development and therapy
journal, March 2017
- Wu, Guiling; Ma, Zhiqiang; Hu, Wei
- Cell Death & Disease, Vol. 8, Issue 3
Reprogramming the immunological microenvironment through radiation and targeting Axl
journal, December 2016
- Aguilera, Todd A.; Rafat, Marjan; Castellini, Laura
- Nature Communications, Vol. 7, Issue 1
The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer
journal, November 2014
- Graham, Douglas K.; DeRyckere, Deborah; Davies, Kurtis D.
- Nature Reviews Cancer, Vol. 14, Issue 12
Viral apoptotic mimicry
journal, June 2015
- Amara, Ali; Mercer, Jason
- Nature Reviews Microbiology, Vol. 13, Issue 8
AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells
journal, May 2019
- Kim, Donghwa; Bach, Duc-Hiep; Fan, Yan-Hua
- Cell Death & Disease, Vol. 10, Issue 5
Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity
journal, March 2017
- Kimani, Stanley G.; Kumar, Sushil; Bansal, Nitu
- Scientific Reports, Vol. 7, Issue 1
TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy
journal, March 2017
- Akalu, Yemsratch T.; Rothlin, Carla V.; Ghosh, Sourav
- Immunological Reviews, Vol. 276, Issue 1
A novel human anti‐AXL monoclonal antibody attenuates tumour cell migration
journal, May 2019
- Duan, Yanting; Luo, Longlong; Qiao, Chunxia
- Scandinavian Journal of Immunology, Vol. 90, Issue 2
Hypoxic control of metastasis
journal, April 2016
- Rankin, E. B.; Giaccia, A. J.
- Science, Vol. 352, Issue 6282
The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype-specific therapeutic target for ovarian cancer
journal, October 2016
- Antony, J.; Tan, T. Z.; Kelly, Z.
- Science Signaling, Vol. 9, Issue 448
Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis
journal, June 2018
- Espindola, Milena S.; Habiel, David M.; Narayanan, Rohan
- American Journal of Respiratory and Critical Care Medicine, Vol. 197, Issue 11
Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies
journal, November 2016
- Kariolis, Mihalis S.; Miao, Yu Rebecca; Diep, Anh
- Journal of Clinical Investigation, Vol. 127, Issue 1
Targeting Gas6/TAM in cancer cells and tumor microenvironment
journal, January 2018
- Wu, Guiling; Ma, Zhiqiang; Cheng, Yicheng
- Molecular Cancer, Vol. 17, Issue 1
AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications
journal, November 2019
- Zhu, Chenjing; Wei, Yuquan; Wei, Xiawei
- Molecular Cancer, Vol. 18, Issue 1
The use of decellularised animal tissue to study disseminating cancer cells
journal, November 2018
- Grey, James F. E.; Campbell-Ritchie, Alastair; Everitt, Nicola M.
- Journal of Cell Science, Vol. 132, Issue 4
Soluble AXL as a marker of disease progression and survival in melanoma
journal, January 2020
- Flem-Karlsen, Karine; Nyakas, Marta; Farstad, Inger Nina
- PLOS ONE, Vol. 15, Issue 1
Axl inhibition: a potential road to a novel acute myeloid leukemia therapy?
journal, January 2015
- Janning, Melanie; Ben-Batalla, Isabel; Loges, Sonja
- Expert Review of Hematology, Vol. 8, Issue 2
AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
journal, November 2019
- Yan, Siyang; Vandewalle, Niels; De Beule, Nathan
- Cancers, Vol. 11, Issue 11
Targeting the TAM Receptors in Leukemia
journal, November 2016
- Huey, Madeline; Minson, Katherine; Earp, H.
- Cancers, Vol. 8, Issue 11
The Receptor Tyrosine Kinase AXL in Cancer Progression
journal, November 2016
- Rankin, Erinn; Giaccia, Amato
- Cancers, Vol. 8, Issue 11
Ligand Activation of TAM Family Receptors-Implications for Tumor Biology and Therapeutic Response
journal, November 2016
- Davra, Viralkumar; Kimani, Stanley; Calianese, David
- Cancers, Vol. 8, Issue 12
The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview
journal, October 2018
- Wium, Martha; Paccez, Juliano; Zerbini, Luiz
- Cells, Vol. 7, Issue 10
Dynamics of Axl Receptor Shedding in Hepatocellular Carcinoma and Its Implication for Theranostics
journal, December 2018
- Holstein, Elisa; Binder, Mathias; Mikulits, Wolfgang
- International Journal of Molecular Sciences, Vol. 19, Issue 12
Targeting the TAM Receptors in Leukemia
text, January 2016
- Earp,, Shelton; A., Minson, Katherine; G., Huey, Madeline
- The University of North Carolina at Chapel Hill University Libraries
Engineered ligand-based VEGFR antagonists with increased receptor binding affinity more effectively inhibit angiogenesis: Kapur et al.
journal, February 2017
- Kapur, Shiven; Silverman, Adam P.; Ye, Anne Z.
- Bioengineering & Translational Medicine, Vol. 2, Issue 1
Virus–Receptor Interactions: The Key to Cellular Invasion
journal, August 2018
- Maginnis, Melissa S.
- Journal of Molecular Biology, Vol. 430, Issue 17
Molecular insights of Gas6/TAM in cancer development and therapy
journal, March 2017
- Wu, Guiling; Ma, Zhiqiang; Hu, Wei
- Cell Death & Disease, Vol. 8, Issue 3
Reprogramming the immunological microenvironment through radiation and targeting Axl
journal, December 2016
- Aguilera, Todd A.; Rafat, Marjan; Castellini, Laura
- Nature Communications, Vol. 7, Issue 1
Viral apoptotic mimicry
journal, June 2015
- Amara, Ali; Mercer, Jason
- Nature Reviews Microbiology, Vol. 13, Issue 8
Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity
journal, March 2017
- Kimani, Stanley G.; Kumar, Sushil; Bansal, Nitu
- Scientific Reports, Vol. 7, Issue 1
Target‐Mediated Drug Disposition Pharmacokinetic/Pharmacodynamic Model‐Informed Dose Selection for the First‐in‐Human Study of AVB‐S6‐500
journal, October 2019
- Bonifacio, Laura; Dodds, Michael; Prohaska, David
- Clinical and Translational Science, Vol. 13, Issue 1
AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications
journal, November 2019
- Zhu, Chenjing; Wei, Yuquan; Wei, Xiawei
- Molecular Cancer, Vol. 18, Issue 1
The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer
journal, July 2017
- Uribe, Diana J.; Mandell, Edward K.; Watson, Adam
- PLOS ONE, Vol. 12, Issue 7
Utilizing combinatorial engineering to develop Tie2 targeting antagonistic angiopoetin-2 ligands as candidates for anti-angiogenesis therapy
journal, April 2017
- Shlamkovich, Tomer; Aharon, Lidan; Barton, William A.
- Oncotarget, Vol. 8, Issue 20
Targeting cyclin-dependent kinase 9 by a novel inhibitor enhances radiosensitization and identifies Axl as a novel downstream target in esophageal adenocarcinoma
journal, July 2019
- Veeranki, Omkara Lakshmi; Tong, Zhimin; Dokey, Rashmi
- Oncotarget, Vol. 10, Issue 45
AXL receptor tyrosine kinase as a therapeutic target in NSCLC
journal, April 2015
- Bivona, Trever; Okimoto, Ross
- Lung Cancer: Targets and Therapy
AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
journal, November 2019
- Yan, Siyang; Vandewalle, Niels; De Beule, Nathan
- Cancers, Vol. 11, Issue 11
Targeting the TAM Receptors in Leukemia
journal, November 2016
- Huey, Madeline; Minson, Katherine; Earp, H.
- Cancers, Vol. 8, Issue 11
The Receptor Tyrosine Kinase AXL in Cancer Progression
journal, November 2016
- Rankin, Erinn; Giaccia, Amato
- Cancers, Vol. 8, Issue 11
Ligand Activation of TAM Family Receptors-Implications for Tumor Biology and Therapeutic Response
journal, November 2016
- Davra, Viralkumar; Kimani, Stanley; Calianese, David
- Cancers, Vol. 8, Issue 12
MiR-34a overexpression enhances the inhibitory effect of doxorubicin on HepG2 cells
journal, June 2019
- Zheng, Shun-Zhen; Sun, Ping; Wang, Jian-Ping
- World Journal of Gastroenterology, Vol. 25, Issue 22