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Pyruvate kinase M2 interacts with mammalian sterile 20-like kinase 1 and inhibits tamoxifen-induced apoptosis in human breast cancer cells.

Abstract Tamoxifen has been reported to be associated with antagonism of estrogen-mediated cell growth signaling and activation of estrogen receptor-independent apoptosis events. It has been demonstrated that mammalian sterile 20-like kinase 1 is a direct target of Caspases to amplify the apoptotic signaling pathway. Here, we presented that breast cancer MCF-7 and SKBR3 cells under treatment with 4-hydroxytamoxifen displayed decreased level of pyruvate kinase M2. Western blot results also showed that 4-hydroxytamoxifen induced the activity of pro-apoptotic protein Caspase-3 in MCF-7 and SKBR3 cells, as evidenced by the cleavage of mammalian sterile 20-like kinase 1 substrate in a dose-dependent manner. Co-immunoprecipitation and immunofluorescence experiments were performed to clarify the relationship between pyruvate kinase M2 and mammalian sterile 20-like kinase 1. The results indicated that mammalian sterile 20-like kinase 1 was associated with pyruvate kinase M2 in cultured mammalian cells, and the interaction between mammalian sterile 20-like kinase 1 and pyruvate kinase M2 was decreased in response to 4-hydroxytamoxifen treatment. In addition, knockdown of pyruvate kinase M2 upregulated the level of cleaved Caspase-3 and subsequently facilitated the nuclear translocation of mammalian sterile 20-like kinase 1. Our data further supplemented the extensive functions of pyruvate kinase M2 in mediating breast cancer cell viability by substantially abating the mammalian sterile 20-like kinase 1-mediated apoptosis. In summary, our results identified that mammalian sterile 20-like kinase 1 is a novel downstream target of pyruvate kinase M2, and knockdown of pyruvate kinase M2 contributes apoptosis via promoting nuclear translocation of mammalian sterile 20-like kinase 1 by enhancing Caspase-3-dependent cleavage.
PMID
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Authors

Mayor MeshTerms
Keywords

Caspase-3

Pyruvate kinase M2

apoptosis

breast cancer cells

mammalian sterile 20-like kinase 1

tamoxifen

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




PMID- 28656802
OWN - NLM
STAT- MEDLINE
DA  - 20170628
DCOM- 20170703
LR  - 20170703
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 4
DP  - 2017 Apr
TI  - Pyruvate kinase M2 interacts with mammalian sterile 20-like kinase 1 and inhibits
      tamoxifen-induced apoptosis in human breast cancer cells.
PG  - 1010428317692251
LID - 10.1177/1010428317692251 [doi]
AB  - Tamoxifen has been reported to be associated with antagonism of estrogen-mediated
      cell growth signaling and activation of estrogen receptor-independent apoptosis
      events. It has been demonstrated that mammalian sterile 20-like kinase 1 is a
      direct target of Caspases to amplify the apoptotic signaling pathway. Here, we
      presented that breast cancer MCF-7 and SKBR3 cells under treatment with
      4-hydroxytamoxifen displayed decreased level of pyruvate kinase M2. Western blot 
      results also showed that 4-hydroxytamoxifen induced the activity of pro-apoptotic
      protein Caspase-3 in MCF-7 and SKBR3 cells, as evidenced by the cleavage of
      mammalian sterile 20-like kinase 1 substrate in a dose-dependent manner.
      Co-immunoprecipitation and immunofluorescence experiments were performed to
      clarify the relationship between pyruvate kinase M2 and mammalian sterile 20-like
      kinase 1. The results indicated that mammalian sterile 20-like kinase 1 was
      associated with pyruvate kinase M2 in cultured mammalian cells, and the
      interaction between mammalian sterile 20-like kinase 1 and pyruvate kinase M2 was
      decreased in response to 4-hydroxytamoxifen treatment. In addition, knockdown of 
      pyruvate kinase M2 upregulated the level of cleaved Caspase-3 and subsequently
      facilitated the nuclear translocation of mammalian sterile 20-like kinase 1. Our 
      data further supplemented the extensive functions of pyruvate kinase M2 in
      mediating breast cancer cell viability by substantially abating the mammalian
      sterile 20-like kinase 1-mediated apoptosis. In summary, our results identified
      that mammalian sterile 20-like kinase 1 is a novel downstream target of pyruvate 
      kinase M2, and knockdown of pyruvate kinase M2 contributes apoptosis via
      promoting nuclear translocation of mammalian sterile 20-like kinase 1 by
      enhancing Caspase-3-dependent cleavage.
FAU - Ji, Feihu
AU  - Ji F
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Guo, Bianqin
AU  - Guo B
AD  - 2 Department of Clinical Laboratory, Chongqing Cancer Institute, Chongqing,
      China.
FAU - Wang, Nian
AU  - Wang N
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Zhong, Changli
AU  - Zhong C
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Huang, Liyuan
AU  - Huang L
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Huang, Yunxiu
AU  - Huang Y
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Wei, Lan
AU  - Wei L
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Su, Min
AU  - Su M
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Jiang, Yulin
AU  - Jiang Y
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Jin, Qianni
AU  - Jin Q
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Liu, Yifeng
AU  - Liu Y
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Zhang, Zhiqian
AU  - Zhang Z
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Yang, Junhong
AU  - Yang J
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, China.
FAU - Chen, Tingmei
AU  - Chen T
AD  - 1 Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, 
      Chongqing Medical University, Chongqing, 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  - 0 (Estrogens)
RN  - 0 (Receptors, Estrogen)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (sterile 20-like protein kinase nerve injury-associated kinase)
RN  - EC 2.7.1.40 (Pyruvate Kinase)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - Caspase 3/*genetics/metabolism
MH  - Cell Cycle/drug effects
MH  - Cell Proliferation/drug effects
MH  - Estrogens/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - MCF-7 Cells
MH  - Protein Interaction Maps/drug effects
MH  - Protein Kinases/genetics/*metabolism
MH  - Pyruvate Kinase/genetics/*metabolism
MH  - Receptors, Estrogen/genetics/metabolism
MH  - Signal Transduction/genetics
MH  - Tamoxifen/*administration & dosage
OTO - NOTNLM
OT  - Caspase-3
OT  - Pyruvate kinase M2
OT  - apoptosis
OT  - breast cancer cells
OT  - mammalian sterile 20-like kinase 1
OT  - tamoxifen
EDAT- 2017/06/29 06:00
MHDA- 2017/07/04 06:00
CRDT- 2017/06/29 06:00
AID - 10.1177/1010428317692251 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Apr;39(4):1010428317692251. doi: 10.1177/1010428317692251.