Morozevich G E, Kozlova N I, Susova O Y, Karalkin P A, Berman A E
Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, 119121, Russia.
Biochemistry (Mosc). 2015 Jan;80(1):97-103. doi: 10.1134/S0006297915010113.
Silencing of α2β1 integrin expression significantly promoted anchorage-dependent apoptosis (anoikis) and drastically reduced clonal activity of MCF-7 human breast carcinoma cells. Depletion of α2β1 enhanced the production of apoptotic protein p53 and of inhibitor of cyclin-dependent protein kinases, p27, while downregulating antiapoptotic protein Bcl-2 and multifunctional protein cMyc. Blocking the expression of α2β1 had no effect on activity of protein kinase Akt, but it sharply increased the kinase activity of Erk1/2. Pharmacological inhibition of Erk1/2 had a minor effect on anoikis of control cells, while it reduced anoikis of cells with downregulated α2β1 to the level of control cells. The data show for the first time that integrin α2β1 is implicated in the protection of tumor cells from anoikis through a mechanism based on the inhibition of protein kinase Erk.
α2β1整合素表达的沉默显著促进了锚定依赖性凋亡（失巢凋亡），并大幅降低了MCF-7人乳腺癌细胞的克隆活性。α2β1的缺失增强了凋亡蛋白p53和细胞周期蛋白依赖性蛋白激酶抑制剂p27的产生，同时下调了抗凋亡蛋白Bcl-2和多功能蛋白cMyc。阻断α2β1的表达对蛋白激酶Akt的活性没有影响，但它显著增加了Erk1/2的激酶活性。Erk1/2的药理学抑制对对照细胞的失巢凋亡影响较小，而它将α2β1下调的细胞的失巢凋亡降低到对照细胞的水平。数据首次表明，整合素α2β1通过基于抑制蛋白激酶Erk的机制参与保护肿瘤细胞免受失巢凋亡。
