PMID- 26901856
OWN - NLM
STAT- MEDLINE
DCOM- 20160718
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 2
DP  - 2016
TI  - The Activation of ERK1/2 and JNK MAPK Signaling by Insulin/IGF-1 Is Responsible 
      for the Development of Colon Cancer with Type 2 Diabetes Mellitus.
PG  - e0149822
LID - 10.1371/journal.pone.0149822 [doi]
LID - e0149822
AB  - Previous studies showed that type 2 diabetes mellitus (T2DM) is linked to 
      increased risk of developing colon cancer. Insulin and insulin-like growth factor 
      1 (IGF-1) are increased in patients with T2DM. The increased insulin and IGF-1 
      may be responsible for the developing of colon cancer. In this study, we 
      investigated the effects and mechanisms of insulin and IGF-1 in colon cancer 
      development in vitro and in vivo. Insulin and IGF-1 alone or together elevated 
      proliferation and reduced apoptosis in colon cancer MC38 cells. Meanwhile, 
      insulin and IGF-1 promoted the phosphorylation of extracellular-signal regulated 
      kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Treatment with ERK1/2 or 
      JNK inhibitor in the presence of insulin and IGF-1 significantly decreased B-cell 
      lymphoma 2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) expression and 
      finally increased apoptosis and inhibited the proliferation. Accelerative colon 
      tumor growth was found in a mouse model of T2DM with db/db mice which got high 
      level of endogenous insulin and IGF-1. Furthermore, the inhibition of ERK1/2 or 
      JNK suppressed the development of colon tumor in vivo. These results suggest that 
      the activation of ERK1/2 and JNK signaling by insulin and IGF-1, at least in 
      part, is responsible for the development of colon cancer with T2DM.
FAU - Teng, Jia-An
AU  - Teng JA
AD  - Department of Cadre Medicine, Division of Endocrinology and Metabolism, People's 
      Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
FAU - Wu, San-Gang
AU  - Wu SG
AD  - Department of Radiation Oncology, Xiamen Cancer Center, the First affiliated 
      Hospital of Xiamen University, Xiamen, China.
FAU - Chen, Jia-Xin
AU  - Chen JX
AD  - Department of Radiation Oncology of Clinical Cancer Center, the People's Hospital 
      of Guangxi Zhuang Autonomous Region, Nanning, China.
FAU - Li, Qiang
AU  - Li Q
AD  - Organ Transplantation Center, Department of Surgery, the Second Xiangya Hospital, 
      Central South University, Changsha, China.
FAU - Peng, Fang
AU  - Peng F
AD  - Department of Radiation Oncology, the First Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zhu, Zhou
AU  - Zhu Z
AD  - Department of Gastrointestinal and Peripheral Vascular Surgery, the People's 
      Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
FAU - Qin, Jian
AU  - Qin J
AD  - Department of Radiation Oncology of Clinical Cancer Center, the People's Hospital 
      of Guangxi Zhuang Autonomous Region, Nanning, China.
FAU - He, Zhen-Yu
AU  - He ZY
AD  - Sun Yat-sen University Cancer Center, State Key laboratory of Oncology in South 
      China, Department of Radiation Oncology, Collaborative Innovation Center of 
      Cancer Medicine, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160222
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blood Glucose/drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Colonic Neoplasms/*etiology/*metabolism
MH  - Diabetes Mellitus, Type 2/genetics/metabolism
MH  - Insulin/metabolism/*pharmacology
MH  - Insulin-Like Growth Factor I/metabolism/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/genetics/*metabolism
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Mice
MH  - bcl-2-Associated X Protein/genetics/metabolism
PMC - PMC4763097
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/02/24 06:00
MHDA- 2016/07/19 06:00
PMCR- 2016/02/22
CRDT- 2016/02/23 06:00
PHST- 2015/04/27 00:00 [received]
PHST- 2016/02/04 00:00 [accepted]
PHST- 2016/02/23 06:00 [entrez]
PHST- 2016/02/24 06:00 [pubmed]
PHST- 2016/07/19 06:00 [medline]
PHST- 2016/02/22 00:00 [pmc-release]
AID - PONE-D-15-18224 [pii]
AID - 10.1371/journal.pone.0149822 [doi]
PST - epublish
SO  - PLoS One. 2016 Feb 22;11(2):e0149822. doi: 10.1371/journal.pone.0149822. 
      eCollection 2016.