Aberrant Expression of proPTPRN2 in Cancer Cells Confers Resistance to Apoptosis.
Aberrant Expression of proPTPRN2 in Cancer Cells Confers Resistance to Apoptosis.
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DOI：
10.1158/0008-5472.can-14-2718
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发表时间：
2015-05-01
期刊：
影响因子：
11.2
通讯作者：
Chen J
中科院分区：
文献类型：
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作者：
Sorokin AV;Nair BC;Wei Y;Aziz KE;Evdokimova V;Hung MC;Chen J
蛋白酪氨酸磷酸酶受体PTPRN2主要在内分泌和神经细胞中表达，在内分泌和神经细胞中发挥胞吐作用。我们发现它的未成熟异构体proPTPRN2在包括乳腺癌在内的各种癌症中过表达。高proPTPRN2表达与淋巴结阳性乳腺癌和不良临床预后密切相关。在小鼠乳腺癌细胞中缺失proPTPRN2促进细胞凋亡并阻断肿瘤形成，而在未转化的人乳腺上皮细胞中强化表达proPTPRN2则起到相反的作用。机制研究表明，ProPTPRN2通过与TRAF2的直接相互作用引发了这些作用，TRAF2是多种激酶级联反应的枢纽支架蛋白，包括激活NF-kB的蛋白。总的来说，我们的结果表明PTPRN2是一种新的候选生物标志物和乳腺癌的治疗靶点。
The protein tyrosine phosphatase receptor PTPRN2 is expressed predominantly in endocrine and neuronal cells where it functions in exocytosis. We found that its immature isoform proPTPRN2 is overexpressed in various cancers including breast cancer. High proPTPRN2 expression was associated strongly with lymph node-positive breast cancer and poor clinical outcome. Loss of proPTPRN2 in breast cancer cells promoted apoptosis and blocked tumor formation in mice, while enforced expression of proPTPRN2 in non-transformed human mammary epithelial cells exerted a converse effect. Mechanistic investigations suggested that ProPTPRN2 elicited these effects through direct interaction with TRAF2, a hub scaffold protein for multiple kinase cascades including ones that activate NF-kB. Overall our results suggest PTPRN2 as a novel candidate biomarker and therapeutic target in breast cancer.