PMID- 30942446
OWN - NLM
STAT- MEDLINE
DCOM- 20190820
LR  - 20211204
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 41
IP  - 6
DP  - 2019 Jun
TI  - TRPC5‑induced autophagy promotes the TMZ‑resistance of glioma cells via the 
      CAMMKbeta/AMPKalpha/mTOR pathway.
PG  - 3413-3423
LID - 10.3892/or.2019.7095 [doi]
AB  - Temozolomide (TMZ) is the first choice chemotherapy agent against glioblastoma, 
      but the TMZ chemotherapy resistance has restricted the clinical application. 
      Although autophagy is considered an adaptive response for cell survival under the 
      pressure of chemotherapy and associated with chemotherapy resistance, its 
      initiator and the precise molecular mechanism remains unknown. In the present 
      study, it was determined that TMZ increases the transient receptor potential 
      cation channel subfamily C member 5 (TRPC5) protein expression and the basal 
      autophagy level, and the upregulation of autophagy is mediated by TRPC5 in glioma 
      cells. Additionally, knockdown of TRPC5 upregulated the chemotherapy sensitivity 
      in vitro and in vivo. Furthermore, TRPC5‑small interfering RNA and 
      pharmacological inhibition indicated that the Ca2+/calmodulin dependent protein 
      kinase beta (CaMKKbeta)/AMP‑activated protein kinase alpha (AMPKalpha)/mechanistic target of 
      rapamycin kinase (mTOR) pathway mediates cell survival autophagy during TMZ 
      treatment. In addition, TMZ‑resistant U87/TMZ cells retained a high basal 
      autophagy level, while silence of TRPC5 expression or inhibition of autophagy 
      reversed TMZ resistance. Thus, the present study revealed that TRPC5, an 
      initiator of autophagy, upregulated TMZ resistance via the CaMKKbeta/AMPKalpha/mTOR 
      pathway and this indicated a novel therapeutic site for drug resistance in glioma 
      chemotherapy.
FAU - Zou, Yan
AU  - Zou Y
AD  - Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Chen, Mu
AU  - Chen M
AD  - Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Zhang, Shuai
AU  - Zhang S
AD  - Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Miao, Zeng'li
AU  - Miao Z
AD  - Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Lu, Xiao'jie
AU  - Lu X
AD  - Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Zhao, Xu'dong
AU  - Zhao X
AD  - Department of Neurosurgery, The Affiliated Wuxi No. 2 Hospital of Nanjing Medical 
      University, Wuxi, Jiangsu 214002, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190402
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC5 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 2.7.11.31 (PRKAA1 protein, human)
RN  - YF1K15M17Y (Temozolomide)
MH  - AMP-Activated Protein Kinases/genetics
MH  - Animals
MH  - Autophagy/drug effects
MH  - Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - Glioma/*drug therapy/genetics/pathology
MH  - Humans
MH  - Mice
MH  - RNA, Small Interfering/pharmacology
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/genetics
MH  - TRPC Cation Channels/antagonists & inhibitors/*genetics
MH  - Temozolomide/*administration & dosage
MH  - Xenograft Model Antitumor Assays
EDAT- 2019/04/04 06:00
MHDA- 2019/08/21 06:00
CRDT- 2019/04/04 06:00
PHST- 2018/09/30 00:00 [received]
PHST- 2019/03/20 00:00 [accepted]
PHST- 2019/04/04 06:00 [pubmed]
PHST- 2019/08/21 06:00 [medline]
PHST- 2019/04/04 06:00 [entrez]
AID - 10.3892/or.2019.7095 [doi]
PST - ppublish
SO  - Oncol Rep. 2019 Jun;41(6):3413-3423. doi: 10.3892/or.2019.7095. Epub 2019 Apr 2.