PMID- 26758953
OWN - NLM
STAT- MEDLINE
DCOM- 20170714
LR  - 20220408
IS  - 1874-4702 (Electronic)
IS  - 1874-4672 (Linking)
VI  - 10
IP  - 2
DP  - 2017
TI  - Mevalonate Pathway and Human Cancers.
PG  - 77-85
LID - 10.2174/1874467209666160112123205 [doi]
AB  - Mevalonate (MVA) is synthesized from 3-hydroxy-3-methylglutaryl coenzyme A 
      (HMG-CoA) by HMG-CoA reductase (HMG-CoAR). MVA is further metabolized to farnesyl 
      pyrophosphate (FPP), a precursor of cholesterol and sterols. FPP is also 
      converted to geranylgeranyl pyrophosphate, and these lipids are used for 
      post-translational modification of proteins that are involved in various aspects 
      of tumor development and progression. Many studies showed that the MVA pathway is 
      up-regulated in several cancers such as leukemia, lymphoma, multiple myeloma; as 
      well as breast, hepatic, pancreatic, esophageal and prostate cancers. Several 
      mechanisms may be involved in dysregulation of this pathway. They include p53 
      mutation, a mutation in HMG-CoAR and sterol-regulatory element binding protein 
      (SREBP) cleavage-activating protein SCAP as its regulator, PKB/Akt activation, 
      decreased AMPK activation, and activation of transcription factors such as: SREBP 
      and HIF-1. Statins as inhibitors of MVA pathway might be useful for cancer 
      prevention and/or treatment through their interactions with essential cellular 
      functions, such as cell proliferation and differentiation. Other inhibitors are 
      also designed for inhibition of this key pathway and their mechanism of action 
      was investigated. In the present review, we will first describe about some 
      inhibitors of MVA, including statins that have been suggested for cancer 
      treatment. We will then discuss about the mechanisms involved in MVA 
      dysregulation, especially in cancer.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Bathaie, Seyedeh Zahra
AU  - Bathaie SZ
AD  - Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares 
      University, P.O. Box: 14115-111, Tehran, Iran.
FAU - Ashrafi, Mahboobeh
AU  - Ashrafi M
AD  - Department of Basic Sciences, Faculty of Veterinary Medicine, Shiraz University, 
      Shiraz, Iran.
FAU - Azizian, Mahshid
AU  - Azizian M
AD  - Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Tamanoi, Fuyuhiko
AU  - Tamanoi F
AD  - Department of Microbiology, Immunology and Molecular Genetics, Jonsson 
      Comprehensive Cancer Center, Molecular Biology Institute, University of 
      California, Los Angeles (UCLA), United States.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Mol Pharmacol
JT  - Current molecular pharmacology
JID - 101467997
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - S5UOB36OCZ (Mevalonic Acid)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/*therapeutic use
MH  - Male
MH  - Metabolic Networks and Pathways/drug effects
MH  - Mevalonic Acid/*metabolism
MH  - Mutation
MH  - Neoplasms/*drug therapy/*metabolism
MH  - Protein Processing, Post-Translational/drug effects
OTO - NOTNLM
OT  - Farnesyl pyrophosphate
OT  - HMG-CoA reductase
OT  - MVA dysregulation
OT  - MVA inhibitors
OT  - SREBP
OT  - geranylgeranyl pyrophosphate
OT  - statins
EDAT- 2016/01/14 06:00
MHDA- 2017/07/15 06:00
CRDT- 2016/01/14 06:00
PHST- 2015/07/01 00:00 [received]
PHST- 2015/10/10 00:00 [revised]
PHST- 2015/12/23 00:00 [accepted]
PHST- 2016/01/14 06:00 [pubmed]
PHST- 2017/07/15 06:00 [medline]
PHST- 2016/01/14 06:00 [entrez]
AID - CMP-EPUB-73025 [pii]
AID - 10.2174/1874467209666160112123205 [doi]
PST - ppublish
SO  - Curr Mol Pharmacol. 2017;10(2):77-85. doi: 10.2174/1874467209666160112123205.