PMID- 31160603
OWN - NLM
STAT- MEDLINE
DCOM- 20200622
LR  - 20211204
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 51
IP  - 6
DP  - 2019 Jun 3
TI  - EPHB6 mutation induces cell adhesion-mediated paclitaxel resistance via EPHA2 and 
      CDH11 expression.
PG  - 1-12
LID - 10.1038/s12276-019-0261-z [doi]
LID - 61
AB  - Mutations affect gene functions related to cancer behavior, including cell 
      growth, metastasis, and drug responses. Genome-wide profiling of cancer mutations 
      and drug responses has identified actionable targets that can be utilized for the 
      management of cancer patients. Here, the recapitulation of pharmacogenomic data 
      revealed that the mutation of EPHB6 is associated with paclitaxel resistance in 
      cancer cells. Experimental data confirmed that the EPHB6 mutation induces 
      paclitaxel resistance in various cancer types, including lung, skin, and liver 
      cancers. EPHB6 mutation-induced paclitaxel resistance was mediated by an 
      interaction with EPHA2, which promotes c-Jun N-terminal kinase (JNK)-mediated 
      cadherin 11 (CDH11) expression. We demonstrated that EPHB6-mutated cells acquire 
      cell adhesion-mediated drug resistance (CAM-DR) in association with CDH11 
      expression and RhoA/focal adhesion kinase (FAK) activation. Targeted inhibition 
      of EPHA2 or CDH11 reversed the acquired paclitaxel resistance, suggesting its 
      potential clinical utility. The present results suggest that the EPHB6 mutation 
      and its downstream EPHA2/JNK/CDH11/RhoA/FAK signaling axis are novel diagnostic 
      and therapeutic targets for overcoming paclitaxel resistance in cancer patients.
FAU - Yoon, Sarah
AU  - Yoon S
AD  - Department of Physiology, Ajou University School of Medicine, Suwon, Republic of 
      Korea.
AD  - Department of Biomedical Science, Graduate School, Ajou University, Suwon, 
      Republic of Korea.
FAU - Choi, Ji-Hye
AU  - Choi JH
AD  - Department of Physiology, Ajou University School of Medicine, Suwon, Republic of 
      Korea.
AD  - Department of Biomedical Science, Graduate School, Ajou University, Suwon, 
      Republic of Korea.
FAU - Kim, Sung Joo
AU  - Kim SJ
AD  - Department of Physiology, Ajou University School of Medicine, Suwon, Republic of 
      Korea.
AD  - Department of Biomedical Science, Graduate School, Ajou University, Suwon, 
      Republic of Korea.
FAU - Lee, Eun-Ju
AU  - Lee EJ
AD  - Department of Physiology, Ajou University School of Medicine, Suwon, Republic of 
      Korea.
FAU - Shah, Masaud
AU  - Shah M
AD  - Department of Molecular Science and Technology, Ajou University, Suwon, Republic 
      of Korea.
FAU - Choi, Sangdun
AU  - Choi S
AD  - Department of Molecular Science and Technology, Ajou University, Suwon, Republic 
      of Korea.
FAU - Woo, Hyun Goo
AU  - Woo HG
AD  - Department of Physiology, Ajou University School of Medicine, Suwon, Republic of 
      Korea. hg@ajou.ac.kr.
AD  - Department of Biomedical Science, Graduate School, Ajou University, Suwon, 
      Republic of Korea. hg@ajou.ac.kr.
LA  - eng
GR  - H15C1551/Korea Health Industry Development Institute (KHIDI)/International
GR  - NRF-2017M3A9B6061509/National Research Foundation of Korea (NRF)/International
GR  - NRF-2017M3C9A6047620/National Research Foundation of Korea (NRF)/International
GR  - NRF-2017R1E1A1A01074733/National Research Foundation of Korea (NRF)/International
GR  - NRF-2015R1D1A4A01020022/National Research Foundation of Korea (NRF)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190603
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Cadherins)
RN  - 0 (EPHA2 protein, human)
RN  - 0 (Ephrin-A2)
RN  - 156621-71-5 (osteoblast cadherin)
RN  - EC 2.7.10.1 (EPHB6 protein, human)
RN  - EC 2.7.10.1 (Receptor, EphA2)
RN  - EC 2.7.10.1 (Receptors, Eph Family)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*pharmacology/therapeutic use
MH  - Cadherins/*genetics
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm
MH  - Ephrin-A2/*genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Neoplasms/*drug therapy/genetics
MH  - Paclitaxel/*pharmacology/therapeutic use
MH  - Receptor, EphA2
MH  - Receptors, Eph Family/*genetics
PMC - PMC6547695
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/06/05 06:00
MHDA- 2020/06/23 06:00
PMCR- 2019/06/03
CRDT- 2019/06/05 06:00
PHST- 2018/10/17 00:00 [received]
PHST- 2019/02/18 00:00 [accepted]
PHST- 2019/01/31 00:00 [revised]
PHST- 2019/06/05 06:00 [entrez]
PHST- 2019/06/05 06:00 [pubmed]
PHST- 2020/06/23 06:00 [medline]
PHST- 2019/06/03 00:00 [pmc-release]
AID - 10.1038/s12276-019-0261-z [pii]
AID - 261 [pii]
AID - 10.1038/s12276-019-0261-z [doi]
PST - epublish
SO  - Exp Mol Med. 2019 Jun 3;51(6):1-12. doi: 10.1038/s12276-019-0261-z.