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EphA4 promotes cell proliferation and cell adhesion-mediated drug resistance via the AKT pathway in multiple myeloma.

Abstract Eph receptor A4 (EphA4), a member of the erythropoietin-producing hepatocellular (Eph) family, has been reported to upregulate in several tumors. However, the role of EphA4 in multiple myeloma has not been clarified yet. In this study, we found that EphA4 promoted proliferation of multiple myeloma cells via the regulation of cell cycle. Besides, EphA4 was closely related to cell adhesion of multiple myeloma cells and promoted cell adhesion-mediated drug resistance by enhancing the phosphorylation levels of Akt (p-AKT) expression in multiple myeloma. More interestingly, we discovered that EphA4 can interact with cyclin-dependent kinase 5 (CDK5) and regulate its expression in multiple myeloma. CDK5 has been reported to be overexpressed in multiple myeloma which mediated bortezomib resistance and also participated in AKT pathway. And we have also proved the fact. So, we supposed that EphA4 interacted with CDK5 and promoted its expression which in turn enhanced p-AKT expression and promoted cell adhesion-mediated drug resistance in multiple myeloma. Therefore, this study clarifies the molecular mechanism of cell adhesion-mediated drug resistance and may be useful in identifying potential target for treatment of multiple myeloma.
PMID
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Authors

Mayor MeshTerms
Keywords

CAM-DR

CDK5

EphA4

Multiple myeloma

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28351297
OWN - NLM
STAT- MEDLINE
DA  - 20170329
DCOM- 20170407
LR  - 20170407
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 3
DP  - 2017 Mar
TI  - EphA4 promotes cell proliferation and cell adhesion-mediated drug resistance via 
      the AKT pathway in multiple myeloma.
PG  - 1010428317694298
LID - 10.1177/1010428317694298 [doi]
AB  - Eph receptor A4 (EphA4), a member of the erythropoietin-producing hepatocellular 
      (Eph) family, has been reported to upregulate in several tumors. However, the
      role of EphA4 in multiple myeloma has not been clarified yet. In this study, we
      found that EphA4 promoted proliferation of multiple myeloma cells via the
      regulation of cell cycle. Besides, EphA4 was closely related to cell adhesion of 
      multiple myeloma cells and promoted cell adhesion-mediated drug resistance by
      enhancing the phosphorylation levels of Akt (p-AKT) expression in multiple
      myeloma. More interestingly, we discovered that EphA4 can interact with
      cyclin-dependent kinase 5 (CDK5) and regulate its expression in multiple myeloma.
      CDK5 has been reported to be overexpressed in multiple myeloma which mediated
      bortezomib resistance and also participated in AKT pathway. And we have also
      proved the fact. So, we supposed that EphA4 interacted with CDK5 and promoted its
      expression which in turn enhanced p-AKT expression and promoted cell
      adhesion-mediated drug resistance in multiple myeloma. Therefore, this study
      clarifies the molecular mechanism of cell adhesion-mediated drug resistance and
      may be useful in identifying potential target for treatment of multiple myeloma.
FAU - Ding, Linlin
AU  - Ding L
AD  - 1 Department of Hematology, Affiliated Hospital of Nantong University, Nantong
      University, Nantong, People's Republic of China.
FAU - Shen, Yaodong
AU  - Shen Y
AD  - 1 Department of Hematology, Affiliated Hospital of Nantong University, Nantong
      University, Nantong, People's Republic of China.
FAU - Ni, Jing
AU  - Ni J
AD  - 1 Department of Hematology, Affiliated Hospital of Nantong University, Nantong
      University, Nantong, People's Republic of China.
FAU - Ou, Yiqing
AU  - Ou Y
AD  - 1 Department of Hematology, Affiliated Hospital of Nantong University, Nantong
      University, Nantong, People's Republic of China.
FAU - Ou, Yangyu
AU  - Ou Y
AD  - 2 Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target,
      Nantong University, Nantong, People's Republic of China.
FAU - Liu, Hong
AU  - Liu H
AD  - 1 Department of Hematology, Affiliated Hospital of Nantong University, Nantong
      University, Nantong, People's Republic of China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 2.7.10.1 (Receptor, EphA4)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.22 (CDK5 protein, human)
SB  - IM
MH  - Bortezomib/administration & dosage
MH  - Cell Adhesion/genetics
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cyclin-Dependent Kinase 5/*biosynthesis/genetics
MH  - Drug Resistance, Neoplasm/genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Multiple Myeloma/*genetics/pathology
MH  - Oncogene Protein v-akt/biosynthesis/*genetics
MH  - Phosphorylation
MH  - Receptor, EphA4/biosynthesis/*genetics
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - CAM-DR
OT  - CDK5
OT  - EphA4
OT  - Multiple myeloma
EDAT- 2017/03/30 06:00
MHDA- 2017/04/08 06:00
CRDT- 2017/03/30 06:00
AID - 10.1177/1010428317694298 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Mar;39(3):1010428317694298. doi: 10.1177/1010428317694298.

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