Cytosolic TMEM88 promotes triple-negative breast cancer by interacting with Dvl.
Cytosolic TMEM88 promotes triple-negative breast cancer by interacting with Dvl.
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胞质 TMEM88 通过与 Dvl 相互作用促进三阴性乳腺癌。
DOI：
10.18632/oncotarget.4379
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发表时间：
2015-09-22
期刊：
影响因子：
--
通讯作者：
Jin F
中科院分区：
文献类型：
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作者：
Yu X;Zhang X;Zhang Y;Jiang G;Mao X;Jin F
TMEM88是一种新发现的定位于细胞膜上的蛋白质，它抑制典型的Wnt信号转导。对139例乳腺癌组织(三阴性癌和75例非三阴性癌)的免疫组织化学分析表明，TMEM88在乳腺癌组织中的表达(71.22%，99/139)明显高于正常乳腺组织(11.4%，4/35；P<；0.001)。TMEM88在三阴性乳腺癌组织中的胞浆和胞核阳性表达率分别为57.81%和9.37%，在非三阴性乳腺癌组织中分别为52%和33.33%(p=0.50和p=0.001)。Western印迹分析表明，TMEM88通过与脱发蛋白(DVL)相互作用促进Snail的表达，抑制Zo-1和occludin的表达，从而刺激乳腺癌的侵袭和转移。而胞浆TMEM88不影响典型的Wnt信号转导，该蛋白的胞浆定位分别与ALL分期(p=0.038和p<；0.001)和淋巴结转移(p=0.01和p=0.002)呈正相关，并通过与DVLS相互作用刺激细胞侵袭。同时，TMEM88的核定位与淋巴结转移呈负相关(p=0.046)。最后，与三重阴性组织相比，TMEM88在非三重阴性组织中的核定位发生率增加，这表明TMEM88的生物学作用因亚细胞定位而异。
TMEM88, a newly discovered protein localized on the cell membrane, inhibits canonical Wnt signaling. Immunohistochemic alanalysis of 139 breast cancers pecimens(64 triple-negative cancers and 75 non-triple-negative cancers) indicated that TMEM88 is expressed at significantly higher levels in breast cancer tissues (71.22%, 99/139) than in normal breast tissues (11.4%, 4/35; p < 0.001). The cytosolic and nuclear expression rates of TMEM88 were 57.81% and 9.37% in triple-negative and 52% and 33.33% (p = 0.5 and p = 0.001) in the non-triple-negative breast cancer tissues, respectively. Western blot analyses indicated that TMEM88 promoted Snail expression and inhibited Zo-1 and Occludin expression by interacting with dishevelled (Dvl) proteins, thereby stimulating invasion and metastasis in breast cancer. While cytosolic TMEM88 did not affect canonical Wnt signaling, cytosolic localization of this protein was positively correlated with both advanced TNM stage (p = 0.038 and p < 0.001) and lymph node metastasis (p = 0.01 and p = 0.002) in all and triple-negative specimens, respectively, and stimulated cell invasion by interacting with Dvls. Meanwhile, nuclear localization of TMEM88 was negatively correlated with lymph node metastasis (p = 0.046). Lastly, the increased prevalence of TMEM88 nuclear localization observed in non-triple-negative, compared to triple-negative tissues, suggests that the biological roles of TMEM88 differ depending on the subcellular localization.