Molecular Pathways: AXL, a Membrane Receptor Mediator of Resistance to Therapy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
M ScaltritiJose Baselga

Abstract

AXL is a tyrosine kinase membrane receptor that signals via PI3K, MAPK, and protein kinase C (PKC), among other pathways. AXL has oncogenic potential and interacts with other membrane receptors, depending on their relative abundance and availability. The increased expression of AXL in cancer is often the result of pharmacologic selective pressure to a number of chemotherapies and targeted therapies and acts as a mechanism of acquired drug resistance. This resistance phenotype, frequently accompanied by epithelial-to-mesenchymal transition, can be reversed by AXL inhibition. In tumors with high levels of EGFR, including lung, head and neck, and triple-negative breast cancer, AXL dimerizes with this receptor and initiates signaling that circumvents the antitumor effects of anti-EGFR therapies. Likewise, AXL overexpression and dimerization with EGFR can overcome PI3K inhibition by activating the phospholipase C-γ-PKC cascade that, in turn, sustains mTORC1 activity. The causative role of AXL in inducing drug resistance is underscored by the fact that the suppression of AXL restores sensitivity to these agents. Hence, these observations indicate that AXL is selectively expressed in tumor cells refractory to therapy and that cotarget...Continue Reading

References

Dec 15, 2000·Oncogene·D R RobinsonS F Lin
Dec 10, 2002·Biochemical and Biophysical Research Communications·Sassan HafiziBjörn Dahlbäck
Apr 9, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sassan HafiziBjörn Dahlbäck
Jun 17, 2005·Biochemical and Biophysical Research Communications·Paloma Valverde
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Peter VajkoczyAxel Ullrich
Jun 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ron BosePhilip A Cole
Mar 15, 2008·Cancer Research·Yi-Xiang ZhangAxel Ullrich
Apr 19, 2008·Nature Reviews. Immunology·Greg Lemke, Carla V Rothlin
Sep 23, 2010·Cancer Research·Erinn B RankinAmato J Giaccia
Dec 7, 2010·Oncogene·W-B OuJ A Fletcher
Aug 5, 2011·Breast Cancer Research and Treatment·Mark MackiewiczNatasha J Caplen
Sep 22, 2011·Molecular Cancer Therapeutics·Anupam VermaSunil Sharma
Jul 4, 2012·Nature Genetics·Zhenfeng ZhangTrever G Bivona
Oct 24, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lauren Averett ByersJohn V Heymach
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Nov 5, 2013·Cold Spring Harbor Perspectives in Biology·Greg Lemke
Apr 29, 2014·Cancer Discovery·David J KonieczkowskiLevi A Garraway
Aug 16, 2014·Cancer Research·Catherine WilsonJeff Settleman
Aug 20, 2014·Cancer Research·Toni M BrandDeric L Wheeler
Oct 22, 2014·Molecular and Cellular Biology·Afnan Abu-ThuraiaJean-François Côté

❮ Previous
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Citations

Oct 27, 2017·Nature Reviews. Cancer·Julia Rotow, Trever G Bivona
Aug 23, 2017·Future Oncology·Aikaterini EmmanouilidiMarco Falasca
Dec 31, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yinzhong LuFang Wu
Apr 12, 2020·Journal of Cellular and Molecular Medicine·Nan WuZhihong Wu
Nov 24, 2016·Oncotarget·Marialuisa SensiAntonella Tomassetti
Jul 9, 2020·Scandinavian Journal of Immunology·Anna K Winge-MainElse Marit Inderberg
Mar 3, 2017·Current Oncology Reports·Marie Schoumacher, Mike Burbridge
May 24, 2016·International Journal of Oncology·Atsushi OkatoNaohiko Seki
Jul 6, 2017·Cancers·Jianrong Lu, Anitha K Shenoy
Dec 9, 2016·Journal of Molecular Cell Biology·Anna de PoloZhi-Min Yuan
Sep 24, 2020·Journal of Experimental & Clinical Cancer Research : CR·Diana CoralloSanja Aveic
Oct 1, 2020·Targeted Oncology·Mitchell S von ItzsteinMuhammad Shaalan Beg
Sep 30, 2017·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yuji OtsukiYoshimi Arima
Apr 20, 2019·International Journal of Molecular Sciences·Teresa Alonso-GordoaJavier Molina-Cerrillo
Mar 21, 2017·European Journal of Nuclear Medicine and Molecular Imaging·Martin PoolMarjolijn N Lub-de Hooge
Jan 10, 2020·PloS One·Karine Flem-KarlsenGunhild Mari Mælandsmo
Sep 28, 2016·Molecular Cancer Research : MCR·Kavitha BalajiKhandan Keyomarsi
Apr 12, 2017·Molecular Cancer Therapeutics·Pol Gimenez-XavierMontse Sanchez-Cespedes
Nov 18, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yanli JinJingxuan Pan
Dec 15, 2017·Molecular Cancer Therapeutics·Paola MagnaghiAntonella Isacchi
Nov 14, 2020·International Journal of Molecular Sciences·Italia FalconeLudovica Ciuffreda
Jul 3, 2017·Biochemical and Biophysical Research Communications·Hanshuang ShaoAlan Wells

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