跳转至内容
Merck
  • PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation.

PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation.

Cancer cell international (2015-03-10)
Xiaoyan Dou, Jing Wei, Aiqin Sun, Genbao Shao, Chandra Childress, Wannian Yang, Qiong Lin
摘要

PDZ binding-kinase (PBK) (also named T-lymphokine-activated killer cell-originated protein kinase (TOPK)), a serine/threonine kinase, is tightly controlled in normal tissues but elevated in many tumors, and functions in tumorigenesis and metastasis. However, the signaling that regulates expression of PBK in cancer cells remains elusive. Here we show that atorvastatin (Lipitor), an inhibitor of hydroxymethylglutaryl co-enzyme A (HMG-CoA) reductase that is a rate-limiting enzyme of mevalonate pathway, down-regulates expression of PBK by impairing protein geranylgeranylation. The shRNA knockdown demonstrated that Yes-associated protein (YAP) mediates geranylgeranylation-regulated expression of PBK. Importantly, atorvastatin or the geranylgeranyltransferase I inhibitor GGTI-298 inhibited breast cancer cell proliferation through inactivation of YAP signaling and down-regulation of PBK. These findings have defined a new signaling pathway that regulated expression of PBK and identified PBK as a downstream target of the Hippo-YAP signaling, uncoverd a mechanism underlying the anti-cancer effect by inhibition of mevalonate pathway and geranylgeranylation, and provided a potential target for breast cancer targeted therapy.

材料
货号
品牌
产品描述

Sigma-Aldrich
十二烷基硫酸钠, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sigma-Aldrich
十二烷基硫酸钠, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
十二烷基硫酸钠 溶液, BioUltra, for molecular biology, 10% in H2O
Sigma-Aldrich
十二烷基硫酸钠 溶液, BioUltra, for molecular biology, 20% in H2O
Sigma-Aldrich
十二烷基硫酸钠, BioUltra, for molecular biology, ≥99.0% (GC)
Supelco
十二烷基硫酸钠, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
十二烷基硫酸钠, ≥98.0% (GC)
Sigma-Aldrich
十二烷基硫酸钠, ACS reagent, ≥99.0%
USP
阿托伐他汀钙, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
香叶基香叶醇, ≥85% (GC)
Sigma-Aldrich
十二烷基硫酸钠, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
十二烷基硫酸钠, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Sigma-Aldrich
十二烷基硫酸钠, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
十二烷基硫酸钠, 92.5-100.5% based on total alkyl sulfate content basis
Supelco
十二烷基硫酸钠, suitable for ion pair chromatography, LiChropur, ≥99.0%
Supelco
阿托伐他汀钙, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
十二烷基硫酸钠, ≥90% ((Assay))
Sigma-Aldrich
GGTI 298 trifluoroacetate salt hydrate, ≥90% (HPLC), film
Sigma-Aldrich
十二烷基硫酸钠, ≥99.0%
月桂基硫酸钠, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
十二烷基硫酸钠, SAJ special grade, ≥97.0%
Sigma-Aldrich
HI-TOPK-032, ≥98% (HPLC)
Sigma-Aldrich
十二烷基硫酸钠, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC), free-flowing, Redi-Dri