Oncogene:在前列腺癌细胞中,CXCR4和PI4KIIIα之间的一个新的cross-talk研究

2018-08-27 AlexYang MedSci原创

趋化因子信号调控细胞迁移和肿瘤的转移。CXCL12是趋化因子家族中的一个成员,并且它的受体CXCR4是一个G蛋白偶联受体(GPCR),均是前列腺癌(PC)骨转移中的关键调控子。在PC细胞中,雄激素能够激活CXCR4基因的表达和脂质筏上的受体信号,从而诱导蛋白酶的表达和癌细胞的侵入。为了鉴定新的支持侵入/转移的脂质筏相关的CXCR4调控因子,研究人员对脂质筏进行了基于SILAC的定量蛋白组分析,材料

趋化因子信号调控细胞迁移和肿瘤的转移。CXCL12是趋化因子家族中的一个成员,并且它的受体CXCR4是一个G蛋白偶联受体(GPCR),均是前列腺癌(PC)骨转移中的关键调控子。在PC细胞中,雄激素能够激活CXCR4基因的表达和脂质筏上的受体信号,从而诱导蛋白酶的表达和癌细胞的侵入。为了鉴定新的支持侵入/转移的脂质筏相关的CXCR4调控因子,研究人员对脂质筏进行了基于SILAC的定量蛋白组分析,材料来源于CXCR4超表达和敲除PC3稳定细胞系。

研究鉴定了进化保守的磷脂酰肌醇4-激酶IIIα(PI4KIIIα)、SAC1磷酸化酶能够去磷酸化磷脂酰肌醇-4磷酸盐,并作为候选的CXCR4调控因子。CXCR4能够与PI4KIIIα在互作,并且能够将其招募到质膜上来产生PI4P。与上述互作一致,研究发现PI4KIIIα能够与CXCR4紧密的连接,并能诱导PC细胞侵入。因此,PI4KIIIα在CXCR4表达的PC3细胞中的敲除能够减少对许多种类趋化因子诱导的入侵响应。在CXCR4表达细胞中的免疫荧光显微分析阐释了PI4P在入侵预测位置的局部产生。人类肿瘤研究关于PI4KIIIα表达在转移性肿瘤中的增加的阐释进一步支持了PI4KIIIα在肿瘤转移中的作用。进一步的是,研究人员同样鉴定了PI4KIIIα在GPCR信号中的一个新的功能,即CXCR4能够调控PI4KIIIα活性和调节肿瘤转移。

最后,研究人员指出,在促进肿瘤转移方面,他们在CXCR4和PI4KIIIα之间鉴定了一个新的cross-talk,并且表明了PI4KIIIα的药理学靶标也许对晚期前列腺癌的治疗具有作用。

原始出处:

Diego Sbrissa, Louie Semaan, Barani Govindarajan et al. A novel cross-talk between CXCR4 and PI4KIIIα in prostate cancer cells. Oncogene. 15 Aug 2018.

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    2018-09-11 juliusluan78
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    2018-08-30 哈哈869

    学习了

    0

  5. 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authenticateStatus=null, createdAvatar=null, createdBy=e09820091072, createdName=lifestar, createdTime=Wed Aug 29 13:35:00 CST 2018, time=2018-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341457, encodeId=0a1834145e93, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160304/IMG56D94856B1B5D6405.jpg, createdBy=27931687771, createdName=一个字-牛, createdTime=Tue Aug 28 13:29:32 CST 2018, time=2018-08-28, status=1, ipAttribution=)]
    2018-08-29 yxch36
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    2018-08-29 lsndxfj
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content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Wed Aug 29 13:35:00 CST 2018, time=2018-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620237, encodeId=578c162023e93, content=<a href='/topic/show?id=c62132549a5' target=_blank style='color:#2F92EE;'>#前列腺癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32549, encryptionId=c62132549a5, topicName=前列腺癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e09820091072, createdName=lifestar, createdTime=Wed Aug 29 13:35:00 CST 2018, time=2018-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341457, encodeId=0a1834145e93, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160304/IMG56D94856B1B5D6405.jpg, createdBy=27931687771, createdName=一个字-牛, createdTime=Tue Aug 28 13:29:32 CST 2018, time=2018-08-28, status=1, ipAttribution=)]
    2018-08-29 chenwq09
  8. 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  9. 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  10. 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    2018-08-28 一个字-牛

    学习了谢谢分享

    0

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