Therapeutic aspects of the Axl/Gas6 molecular system

被引:31
作者
Di Stasi, Rossella [1 ]
De Rosa, Lucia [1 ]
D'Andrea, Luca D. [2 ]
机构
[1] CNR, Ist Biostrutture & Bioimmagini, Via Mezzocannone 16, I-80134 Naples, Italy
[2] CNR, Ist Biostrutture & Bioimmagini, Via Nizza 52, I-10126 Turin, Italy
关键词
RECEPTOR TYROSINE KINASE; MYELOID-LEUKEMIA CELLS; ARREST-SPECIFIC GENE-6; GROWTH-FACTOR RECEPTOR; ZIKA VIRUS-INFECTION; PROTEIN; 6; GAS6; AXL KINASE; TAM RECEPTORS; TUMOR-GROWTH; PLASMA-CONCENTRATIONS;
D O I
10.1016/j.drudis.2020.09.022
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Axl receptor tyrosine kinase (RTK) and its ligand, growth arrest-specific protein 6 (Gas6), are involved in several biological functions and participate in the development and progression of a range of malignancies and autoimmune disorders. In this review, we present this molecular system from a drug discovery perspective, highlighting its therapeutic implications and challenges that need to be addressed. We provide an update on Axl/Gas6 axis biology, exploring its role in fields ranging from angiogenesis, cancer development and metastasis, immune response and inflammation to viral infection. Finally, we summarize the molecules that have been developed to date to target the Axl/Gas6 molecular system for and
引用
收藏
页码:2130 / 2148
页数:19
相关论文
共 177 条
[51]   The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer [J].
Graham, Douglas K. ;
DeRyckere, Deborah ;
Davies, Kurtis D. ;
Earp, H. Shelton .
NATURE REVIEWS CANCER, 2014, 14 (12) :769-785
[52]   Targeted GAS6 Delivery to the CNS Protects Axons from Damage during Experimental Autoimmune Encephalomyelitis [J].
Gruber, Ross C. ;
Ray, Alex K. ;
Johndrow, Christopher T. ;
Guzik, Hillary ;
Burek, Dominika ;
Garcia de Frutos, Pablo ;
Shafit-Zagardo, Bridget .
JOURNAL OF NEUROSCIENCE, 2014, 34 (49) :16320-16335
[53]   Profile of cabozantinib and its potential in the treatment of advanced medullary thyroid cancer [J].
Hart, Christopher D. ;
De Boer, Richard H. .
ONCOTARGETS AND THERAPY, 2013, 6 :1-7
[54]   The role of γ-carboxylation in the anti-apoptotic function of gas6 [J].
Hasanbasic, I ;
Rajotte, I ;
Blostein, M .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2005, 3 (12) :2790-2797
[55]   Loss of the TAM Receptor Axl Ameliorates Severe Zika Virus Pathogenesis and Reduces Apoptosis in Microglia [J].
Hastings, Andrew K. ;
Hastings, Katherine ;
Uraki, Ryuta ;
Hwang, Jesse ;
Gaitsch, Nellie ;
Dhaliwal, Khushwant ;
Williamson, Eric ;
Fikrig, Erol .
ISCIENCE, 2019, 13 :339-+
[56]   TAM Receptors Are Not Required for Zika Virus Infection in Mice [J].
Hastings, Andrew K. ;
Yockey, Laura J. ;
Jagger, Brett W. ;
Hwang, Jesse ;
Uraki, Ryuta ;
Gaitsch, Hallie F. ;
Parnell, Lindsay A. ;
Cao, Bin ;
Mysorekar, Indira U. ;
Rothlin, Carla V. ;
Fikrig, Erol ;
Diamond, Michael S. ;
Iwasaki, Akiko .
CELL REPORTS, 2017, 19 (03) :558-568
[57]   Gas 6 promotes Axl-mediated survival in pulmonary endothelial cells [J].
Healy, AM ;
Schwartz, JJ ;
Zhu, XH ;
Herrick, BE ;
Varnum, B ;
Farber, HW .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2001, 280 (06) :L1273-L1281
[58]   Growth arrest-specific protein-6/AXL signaling induces preeclampsia in rats [J].
Hirschi, Kelsey M. ;
Tsai, Kary Y. F. ;
Davis, Taylor ;
Clark, J. Christian ;
Knowlton, M. Nekel ;
Bikman, Benjamin T. ;
Reynolds, Paul R. ;
Arroyo, Juan A. .
BIOLOGY OF REPRODUCTION, 2020, 102 (01) :199-210
[59]   Axl-/- mice have delayed recovery and prolonged axonal damage following cuprizone toxicity [J].
Hoehn, Hannah J. ;
Kress, Yvonne ;
Sohn, Albert ;
Brosnan, Celia F. ;
Bourdon, Sarah ;
Shafit-Zagardo, Bridget .
BRAIN RESEARCH, 2008, 1240 :1-11
[60]   R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer [J].
Holland, Sacha J. ;
Pan, Alison ;
Franci, Christian ;
Hu, Yuanming ;
Chang, Betty ;
Li, Weiqun ;
Duan, Matt ;
Torneros, Allan ;
Yu, Jiaxin ;
Heckrodt, Thilo J. ;
Zhang, Jing ;
Ding, Pingyu ;
Apatira, Ayodele ;
Chua, Joanne ;
Brandt, Ralf ;
Pine, Polly ;
Goff, Dane ;
Singh, Rajinder ;
Payan, Donald G. ;
Hitoshi, Yasumichi .
CANCER RESEARCH, 2010, 70 (04) :1544-1554