[转帖]信号传递：EGFR能维持细胞的存活
消息来源：<a href="http://www.lifeomics.com">www.lifeomics.com</a><hr width="98%" size="1"/><p> </p><p><img width="180" height="236" align="left" alt="" src="http://www.lifeomics.com/image/image_gallery?img_id=33019"/></p><p class="MsoNormal"><span style="font-family: 宋体;"> <font face="Times New Roman"> </font></span></p><p class="MsoNormal"> </p><p class="MsoNormal"><span style="font-family: 宋体;"><font face="Times New Roman"> <strong>图片来源：</strong></font></span><font face="Times New Roman"><strong><span lang="EN-US">BRANDX</span></strong></font></p><p class="MsoNormal"> </p><p class="MsoNormal"> </p><p class="MsoNormal"> </p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><strong><span style="font-family: 宋体;"> 研究人员发现上皮生长因子受体（</span><span lang="EN-US">epidermal growth factor receptor, EGFR</span></strong><strong><span style="font-family: 宋体;">）能够阻止自吞噬现象的发生、维持细胞内葡萄糖的代谢水平，从而提高细胞存活率。这一作用不具有激酶依赖性，进而解释了</span><span lang="EN-US">EGFR</span></strong><strong><span style="font-family: 宋体;">抑制剂对癌症病人不起作用的原理。</span><span lang="EN-US"><op></op></span></strong></font></p>
<p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US"><op> </op></span></font></p><p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US"><op></op></span></font></p><p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US"><op></op></span></font></p><p class="MsoNormal"> </p><p class="MsoNormal"> </p><p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US"><op></op></span></font></p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><span style="font-family: 宋体;"> 在癌症治疗中，人们发现使用</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">酪氨酸激酶抑制剂未能起到有效的治疗作用，这让研究人员颇感意外。</span><span lang="EN-US">Zhang Weihua</span><span style="font-family: 宋体;">等人的新发现揭示了这一现象的部分机制：</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">能维持细胞的存活，并且这一功能不具有激酶依赖性。</span></font></p><p class="MsoNormal"> </p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><span style="font-family: 宋体;"> 当细胞内能量来源有限或未能维持必需能量时，就会发生自吞噬现象。</span><span lang="EN-US">Zhang</span><span style="font-family: 宋体;">等人在前列腺癌、乳腺癌和直肠癌细胞系中利用</span><span lang="EN-US">siRNA</span><span style="font-family: 宋体;">特异介导</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">的表达下调，此时癌细胞会发生自吞噬进而死亡。转染了</span><span lang="EN-US">EGFR siRNA</span><span style="font-family: 宋体;">的细胞在经过</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">激酶抑制剂处理后，其葡萄糖水平也会下降约</span><span lang="EN-US">50%</span><span style="font-family: 宋体;">，未转染细胞则能够维持稳定的葡萄糖水平。</span></font></p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><br/></font></p><p class="MsoNormal"><font face="Times New Roman"><span style="font-family: 宋体;"> 那么</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">如何起到稳定细胞内葡萄糖水平的作用呢？</span><span lang="EN-US">Zhang</span><span style="font-family: 宋体;">等人的研究数据表明，</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">的表达能够调节葡萄糖的吸收。他们还发现，与对照组相比，在转染了</span><span lang="EN-US">EGFR siRNA</span><span style="font-family: 宋体;">的细胞内，发生了钠和葡萄糖协同转运蛋白（</span><span lang="EN-US">sodium and glucose cotransporter, SGLT1</span><span style="font-family: 宋体;">）的表达量下调现象。研究人员进而直接干扰</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">的表达，此时细胞会发生与</span><span lang="EN-US">EGFR siRNA</span><span style="font-family: 宋体;">作用后类似的自吞噬现象。通过抑制蛋白酶体活性可以拯救</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">表达缺失时</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">的表达下调，这说明</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">的表达缺失会引起</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">的降解。更重要的是，研究人员还发现不论是野生型的</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">还是激酶缺失突变的</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">都能与</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">发生相互作用。另外，在抗</span><span lang="EN-US">siRNA</span><span style="font-family: 宋体;">干扰的细胞中转染了</span><span lang="EN-US">EGFR siRNA</span><span style="font-family: 宋体;">以后，无论是野生型</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">或是激酶缺失突变的</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">都可以维持</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">的稳定表达。这说明</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">能够使</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">的表达水平维持稳定，且不受激酶活性有无的影响。</span></font></p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><em><span lang="EN-US"><op></op></span></em><br/></font></p><p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US"> Zhang</span><span style="font-family: 宋体;">等人还检测了</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">表达水平不一的癌症细胞对葡萄糖缺乏的敏感性。他们发现，同时表达</span><span lang="EN-US">EGFR </span><span style="font-family: 宋体;">和</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">的癌细胞对于葡萄糖缺乏所诱导的死亡具有耐受性。相反，不表达</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">的癌细胞其</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">表达量较低，这种癌细胞在正常葡萄糖浓度下未能存活，而过表达</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">或者是</span><span lang="EN-US">SGLT1</span><span style="font-family: 宋体;">甚至可以在低葡萄糖水平的情况下提高细胞的存活率。</span></font></p><p class="MsoNormal"> </p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US"> Zhang</span><span style="font-family: 宋体;">等人的研究表明，</span><span lang="EN-US">EGFR-SGLT1</span><span style="font-family: 宋体;">能够使癌细胞内的葡萄糖水平维持在基线以上，从而避免自吞噬的发生并更具生存优势。而之前有研究数据表明，使用</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">激酶抑制剂并不足以诱导细胞死亡的发生或是抑制</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">的所有功能。</span><span lang="EN-US">Zhang</span><span style="font-family: 宋体;">等人的研究成果则有助于解释上述现象。为了取得有效的治疗效果，我们在将来的治疗中必须注意同时抑制</span><span lang="EN-US">EGFR</span><span style="font-family: 宋体;">激酶依赖性的和非激酶依赖性的功能。</span></font></p><p class="MsoNormal"> </p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><span style="font-family: 宋体;">原文检索：</span><a href="http://www.signaling-gateway.org/"><span lang="EN-US">http://www.signaling-gateway.org</span></a></font></p><p class="MsoNormal"> </p><p class="MsoNormal"> </p><p class="MsoNormal"> </p>
<p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US"><op> </op></span><span lang="EN-US">Sirius/</span><span style="font-family: 宋体;">编译</span></font></p><p class="MsoNormal"> </p><p class="MsoNormal"> </p>
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<p class="MsoNormal"><font face="Times New Roman"><span style="font-family: 宋体;">关键词：上皮生长因子受体</span><span lang="EN-US"><span>；</span></span><span style="font-family: 宋体;">钠和葡萄糖协同转运蛋白</span></font></p>
<p class="MsoNormal"><font face="Times New Roman"><span lang="EN-US">Key words</span><span style="font-family: 宋体;">：</span><span lang="EN-US">EGFR<span>；</span>SGLT1</span><strong><span lang="EN-US"><op></op></span></strong></font></p>
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