Statins of gastric cancer, reduce cell migration

Statins are-3-hydroxy-3-methylglutaryl-coenzymeA
reductase (HMG-COAR) inhibitors lead to inhibit cholesterol synthesis and
reduction of the downstream intermediate products that involve in carcinogenesis such as farnesyl pyrophosphate
(FPP) and geranylgeranyl pyrophosphate (GGPP) .Statins include :-
lovastatin , simvastatin ,atrovastatin ,flavastatin , pravastatin and
rosuvastatin calcium. Statins used as hypocholesterolemic drugs in treatment
of dyslipidemia , prevention cardiovascular disease, prevent development
atherosclerosis , decrease low-density lipoprotein (LDL) , stroke myocardial
injury and mortality . There is multi-effect of statins as anti-inflammatory effect
and anti-cancer effect and reduce cancer risk by  firstly ,  decrease level of cholesterol that tumor
cells need it in development and expansion . Secondly , prevent oncogenic proteins
(Ras,Rho,Rac, and Rab) activation . Statins reduce risk of gastric cancer,
reduce cell migration and colony forming of prostate cancer-3 cells in
prostate cancer , pancreatic cancer , esophagus
cancer , hepatocellular
carcinoma, lung cancer, colon cancer , colorectal cancer , improved survival in ovarian cancer and act as
anew possible therapy in breast cancer  , in
DVT( Deep Vein Thrombosis) and PE (Pulmonary embolism) patients statins have
protective influence. Statins inhibit angiogenesis , tumor growth , invasion and
metastasis , induce apoptosis ,reduce adhesion ,E selectin and matrix
metalloproteinase -9 (MMP-9).In CLL patients statin and aspirin enhance cell
apoptosis in addition statins improve response in chemotherapy.Moreover , Statins
reduce risk of hematological malignancies ,f non-hodgkin lymphoma(NHL),
multiple myeloma (MM) also induce apoptosis in CLL ,ALL,AML , MM and IM-9
lymphoblast .Because  the anti-leukemic
effect of statins.  
Wiskott-Aldrch Syndrom (WAS) is a rare X-linked
recessive disorder caused by mutations in the gene for the WAS protein
(WASP). WAS characterized by thrombocytopenia, small platelet size,
autoimmunity and an increased risk of malignancies. WASP family contain WASP
protein and N-WASP also WAVE proteins (WASP-family veprolin-homologous
protein) family contain WAVE1,WAVE2 andWAVE3. WASP proteins present only in
hematopoietic cell but the rest of WASP family and WAVE proteins expressed in
different tissue in addition expressed 
in the cytoplasm of hematopoietic cells.WASP/WAVE proteins are
scaffolds link upstream signals to activate actin- related protein 2 and 3
complex (ARP2/3) via binding with Veprolin/Cofilin/Acidic domain at  C terminus leading to initiate
polymerization of actin cytoskeleton that required for other pathological
modification like cell shap and morphology ,enhance cytokines , cell motility
and progression and metastasis for cancer . The WASP/WAVE proteins work as downstream
effectors to GTPase (Rho,RAS,Cdc42) that control actin polymerization and
involve in cell motility and proliferation in addition WAVE proteins wok as
downstream of Rac to induce formation of plasma membrane protrusion known as
fillopodia and lamellipodia which known as invadpodia in cancer cell. Both Rac
and Cdc-92 active nucleation- promoting factors (NPF) that consist of
WASP,NWASP,WAVE1,WAVE2,WAVE3,WASH,WHAMM,JMY.  WAVE proteins play role in cell migration,  invasion , adhesion , motility and
metastasis that lead to poor prognosis So WAVE proteins identified as
prognostic marker or target for treatment and drug development that will
affect on WAVE signaling pathway.  


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