Cytosolic THUMPD1 promotes breast cancer cells invasion and metastasis via the AKT-GSK3-Snail pathway.
Cytosolic THUMPD1 promotes breast cancer cells invasion and metastasis via the AKT-GSK3-Snail pathway.
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胞质 THUMPD1 通过 AKT-GSK3-Snail 通路促进乳腺癌细胞侵袭和转移
DOI：
10.18632/oncotarget.14528
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发表时间：
2017-02-21
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhang X;Jiang G;Sun M;Zhou H;Miao Y;Liang M;Wang E;Zhang Y
人THUMP结构域蛋白1（THUMP 1）是一种特异性衔接蛋白，通过与NAT 10相互作用调节tRNA乙酰化。对146例乳腺癌标本（82例三阴性和64例非三阴性）的免疫组化分析表明，THUMPD 1在乳腺癌组织中的表达（60.9%，89/146）高于正常乳腺组织（28.3%，15/53; p < 0.001）。乳腺癌中THUMPD 1的总体表达和胞浆表达（而非核表达）与晚期TNM分期（分别为p = 0.003和p < 0.001）、淋巴结转移（分别为p = 0.001和p < 0.001）和患者预后差（分别为p = 0.001和p < 0.001）相关。THUMPD 1与雅普相互作用并共定位，但不影响Hippo通路活性。THUMPD 1过表达增强乳腺癌细胞的侵袭和迁移能力，其机制可能与激活AKT、GSK 3 β和Snail，抑制E-cadherin有关。用AKT抑制剂LY 294002治疗，降低了乳腺癌细胞中THUMPD 1过表达的影响。这些结果表明，THUMPD 1通过AKT-GSK 3 β-Snail途径促进乳腺癌细胞的侵袭和迁移。
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0.003 and p < 0.001, respectively), lymph node metastasis (p = 0.001 and p < 0.001, respectively), and poor patient prognosis (p = 0.001 and p < 0.001, respectively). THUMPD1 interacted and co-localized with YAP, but did not affect Hippo pathway activity. THUMPD1 overexpression enhanced breast cancer cells invasion and migration in vivo and in vitro, possibly through activation of AKT, GSK3β and Snail, and inhibition of E-cadherin. Treatment with the AKT inhibitor, LY294002, reduced the effects of THUMPD1 overexpression in breast cancer cells. These results indicate that THUMPD1 promotes breast cancer cells invasion and migration via the AKT-GSK3β-Snail pathway.