Clinical &Translational Gastroenterology: PFKFB3 过表达在胃癌进展中具有强烈的负面影响

2021-08-16 MedSci原创 MedSci原创

胃癌(GC)的发病率和死亡率在我国恶性肿瘤中位列第三、第二位,严重威胁着居民的身体健康,胃癌细胞的高侵袭性和转移性是胃癌预后不良的主要原因。

      胃癌(GC)的发病率和死亡率在我国恶性肿瘤中位列第三、第二位,严重威胁着居民的身体健康,胃癌细胞的高侵袭性和转移性是胃癌预后不良的主要原因。肿瘤细胞浸润和远处转移需要足够的营养和能量。因此,肿瘤细胞需要通过代谢的重编程来调节能量代谢,包括糖酵解、脂质代谢,以满足快速生长、侵袭和转移的需要。虽然之前的研究表明代谢紊乱是恶性肿瘤的一个重要特征,但代谢改变如何在GC发生并在其肿瘤发生和发展中发挥重要作用尚不清楚。

 

      在 1920 年代,OttoWarburg 等人。发现肿瘤细胞的糖代谢与正常细胞不同。在缺氧甚至有氧条件下,肿瘤细胞以糖酵解为主要提供能量的方式,称为有氧糖酵解或 Warburg 效应。PFKFB3是一种合成果糖2,6-二磷酸(F-2,6-DP)的酶,参与糖酵解,广泛存在于许多细胞中。在所有PFKFB3同工酶中,PFKFB3的活性比二磷酸酶高约700倍。因此,它有利于细胞存活、糖酵解和 F-2,6-DP 合成。因此,本项研究旨在探究PFKFB3过表达在胃癌进展中的作用。

 

      研究人员通过免疫组织化学 (IHC) 在 GC 组织和配对的癌旁组织学正常组织 (PCHNT) 中评估 PFKFB3 表达。然后评估了 PFKFB3 表达与临床特征和 HIF-1α、Ki-67、E-钙粘蛋白、Snail和波形蛋白表达水平的关联。最后通过一系列的体内和体外进行实验来证实PFKFB3对生长,迁移,和GC细胞侵袭的影响。

 

 

      研究结果发现与 PCHNT 相比,GC 组织中 PFKFB3 的表达显着更高(P = 0.0001)。PFKFB3表达与肿瘤大小(P = 0.0001)、分化程度(P = 0.025)、静脉浸润(P = 0.084)、神经浸润(P = 0.014)、淋巴浸润(P = 0.000)、局部浸润(P = 0.000)、浸润深度(P = 0.000)、淋巴结转移(P = 0.000)、肿瘤-淋巴结-转移分期(P = 0.000)和患者存活率(P= 0.000)均有很强的相关性。值得注意的是,PFKFB3 上调与 GC 样品中上皮间质转化 (EMT) 的增加高度相关。PFKFB3 过表达在体外GC 细胞中正向调节细胞增殖、迁移和 EMT ,同时激活 NF-κB 信号传导。NF-κB 抑制剂的给药减弱了 GC 细胞中 PFKFB3 诱导的 EMT。

 

      本项研究证实PFKFB3 可以通过 NF-κB 通路介导的 EMT 增强 GC 细胞的恶性程度,表明 PFKFB3 可能是 GC 未来治疗的潜在靶点。

 

 

原始出处:

Lei, Lan. Et al. A Potential Oncogenic Role for PFKFB3 Overexpression in Gastric Cancer Progression. Clinical and Translational Gastroenterology.2021.

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    2022-06-20 许安
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authenticateStatus=null, createdAvatar=, createdBy=0bed488, createdName=jktdtl, createdTime=Mon Mar 28 11:00:19 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505309, encodeId=694e150530963, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Wed Aug 18 03:00:19 CST 2021, time=2021-08-18, status=1, ipAttribution=)]
    2022-04-28 bsmagic9140
  8. 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time=2022-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958206, encodeId=4bb0195820615, content=<a href='/topic/show?id=48a294126c0' target=_blank style='color:#2F92EE;'>#过表达#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94126, encryptionId=48a294126c0, topicName=过表达)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=19ad38, createdName=lq1767, createdTime=Tue Mar 01 03:00:19 CST 2022, time=2022-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2065420, encodeId=29bf2065420d1, content=<a href='/topic/show?id=94ffe853a7' target=_blank style='color:#2F92EE;'>#Gastroenterol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7853, encryptionId=94ffe853a7, topicName=Gastroenterol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0bed488, createdName=jktdtl, createdTime=Mon Mar 28 11:00:19 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505309, encodeId=694e150530963, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Wed Aug 18 03:00:19 CST 2021, time=2021-08-18, status=1, ipAttribution=)]
    2022-03-01 lq1767
  9. 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研究表明,有一代胃癌家族史可增加近2倍的发生胃癌风险,并且表明不同病理类型以及部位的风险不同,为以后的预防提供帮助。

Gastric Cancer:甘油三酯-葡萄糖指数可以预测胃癌的发生

胃癌是一种多因素、多步骤的疾病,其中环境、宿主和基因是胃癌发生的主要原因。虽然全球的胃癌的发病率有所下降,但目前仍然是最常见的恶性肿瘤之一。