Remodeling of Channel-Forming ORAI Proteins Determines an Oncogenic Switch in Prostate Cancer

被引：192

作者：

Dubois, Charlotte ^{[1
]}

Vanden Abeele, Fabien ^{[1
]}

Lehen'kyi, V'yacheslav ^{[1
]}

Gkika, Dimitra ^{[1
]}

Guarmit, Basma ^{[4
]}

Lepage, Gilbert ^{[1
]}

Slomianny, Christian ^{[1
]}

Borowiec, Anne Sophie ^{[1
]}

Bidaux, Gabriel ^{[1
]}

Benahmed, Mohamed ^{[4
]}

Shuba, Yaroslav ^{[1
,2
,3
]}

Prevarskaya, Natalia ^{[1
]}

机构：

[1] Univ Sci & Technol Lille, Equipe Labellisee Ligue Natl Canc, Lab Excellence Ion Channels Sci & Therapeut, Inserm U1003,SIRIC ONCOLille, F-59656 Villeneuve Dascq, France

[2] Natl Acad Sci Ukraine, Bogomoletz Inst Physiol, UA-01024 Kiev, Ukraine

[3] Natl Acad Sci Ukraine, Int Ctr Mol Physiol, UA-01024 Kiev, Ukraine

[4] Hop Archet, Ctr Mediterraneen Med Mol, INSERM U895, INSERM, F-06202 Nice, France

来源：

CANCER CELL | 2014年 / 26卷 / 01期

关键词：

OPERATED CALCIUM-ENTRY; CA2+ ENTRY; ARACHIDONIC-ACID; EPITHELIAL-CELLS; STIM; PROLIFERATION; PROGRESSION; APOPTOSIS; CYCLE; HOMEOSTASIS;

D O I：

10.1016/j.ccr.2014.04.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

ORAI family channels have emerged as important players in malignant transformation, yet the way in which they reprogram cancer cells remains elusive. Here we show that the relative expression levels of ORAI proteins in prostate cancer are different from that in noncancerous tissue. By mimicking ORAI protein remodeling observed in primary tumors, we demonstrate in in vitro models that enhanced ORAI3 expression favors heteromerization with ORAN to form a novel channel. These channels support store-independent Ca2+ entry, thereby promoting cell proliferation and a smaller number of functional homomeric ORAll -based store-operated channels, which are important in supporting susceptibility to apoptosis. Thus, our findings highlight disrupted dynamic equilibrium of channel-forming proteins as an oncogenic mechanism.

引用

页码：19 / 32

页数：14

共 41 条

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