TY  - JOUR
A1  - DiPrima, Michael
A1  - Wang, Dunrui
A1  - Tröster, Tröster, Alix
A1  - Maric, Dragan
A1  - Terrades-Garcia, Nekane
A1  - Ha, Taekyu
A1  - Kwak, Hyeongil
A1  - Sánchez-Martín, David
A1  - Kudlinzki, Denis
A1  - Schwalbe, Harald
A1  - Tosato, Giovanna
T1  - Identification of eph receptor signaling as a regulator of autophagy and a therapeutic target in colorectal carcinoma
T2  - Molecular oncology
N2  - Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. We report that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells. We find that genetic and biochemical inhibition of Eph tyrosine kinase activity or depletion of the Eph ligand EphrinB2 reproducibly induces colorectal carcinoma cell death by autophagy. Spautin and 3-methyladenine, inhibitors of early steps in the autophagic pathway, significantly reduce autophagy-mediated cell death that follows inhibition of phosphotyrosine-dependent Eph signaling in colorectal cancer cells. A small-molecule inhibitor of the Eph kinase, NVP-BHG712 or its regioisomer NVP-Iso, reduces human colorectal cancer cell growth in vitro and tumor growth in mice. Colorectal cancers express the EphrinB ligand and its Eph receptors at significantly higher levels than numerous other cancer types, supporting Eph signaling inhibition as a potential new strategy for the broad treatment of colorectal carcinoma.
KW  - Eph receptors
KW  - Ephrin ligand
KW  - cell death
KW  - colorectal cancer
KW  - tyrosine kinase signaling
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54956
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-549568
SN  - 1878-0261
SN  - 1574-7891
N1  - This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
VL  - 13
IS  - 11
SP  - 2441
EP  - 2456
PB  - John Wiley & Sons, Inc.
CY  - Hoboken, NJ
ER  -