SPATA2 suppresses epithelial-mesenchymal transition to inhibit metastasis and radiotherapy sensitivity in non-small cell lung cancer via impairing DVL1/β-catenin signaling.
SPATA2 suppresses epithelial-mesenchymal transition to inhibit metastasis and radiotherapy sensitivity in non-small cell lung cancer via impairing DVL1/β-catenin signaling.
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DOI：
10.1111/1759-7714.14828
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发表时间：
2023-04
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
转移是癌症患者癌症相关死亡的主要原因。上皮-间质转化（EMT）是肿瘤转移级联反应中的一个关键过程。EMT是癌细胞从上皮状态转变为间充质状态的发育程序，并赋予转移特性以及治疗抗性。寻找抑制EMT的因素将大大改善患者的预后。精子发生相关蛋白2（Spermatogenesis associated 2，SPATA 2）最初是从人睾丸中分离出来的，并被证明在精子发生中起作用。然而，迄今为止，SPATA 2在肿瘤发生中的作用尚不清楚。在本研究中，通过挖掘公共数据库并在收集的非小细胞肺癌（NSCLC）标本中进行验证，我们发现SPATA 2的表达与患者的预后呈正相关，是NSCLC的独立预后标志物。功能研究表明，SPATA 2的异位过表达抑制EMT，导致体外运动性和侵袭性受损以及体内转移，并增加NSCLC的放射敏感性。机制研究表明，SPATA 2可以通过抑制DVL 1的泛素化来抑制β-catenin信号通路，从而实现其功能。综上所述，本研究揭示了SPATA 2对EMT的抑制作用，SPATA 2可能是NSCLC治疗的潜在靶点。精子发生相关蛋白2（SPATA 2）抑制上皮间质转化，导致非小细胞肺癌转移受损和放射敏感性增加。机制研究表明，SPATA 2与CYLD结合并增强CYLD去泛素化酶活性以减少DVL 1的K63连接的多聚泛素化，这导致DVL 1降解并随后减弱β-连环蛋白信号传导。
Metastasis is the major cause of cancer‐related death of cancer patients. Epithelial‐mesenchymal transition (EMT) is one critical process during the cascade of tumor metastasis. EMT is a developmental program exploited by cancer cells to transition from epithelial state to mesenchymal state and confers metastatic properties as well as treatment resistance. Finding factors to inhibit EMT will greatly improve the prognosis patients. Spermatogenesis associated 2 (SPATA2) was originally isolated from human testis and proved playing a role in spermatogenesis. To date, however, the role of SPATA2 in oncogenesis is unknown. In the current study, by mining the public database and validating in a cohort of collected non–small cell lung cancer (NSCLC) specimens, we uncovered that the expression of SPATA2 positively correlated with the prognosis of patients and was an independent prognosis marker in NSCLC. Functional studies proved that ectopic overexpression of SPATA2 inhibited EMT resulting in impaired motility and invasiveness properties in vitro and metastasis in vivo, and increased radiosensitivity in NSCLC. Mechanistic investigation showed that SPATA2 could suppress the β‐catenin signaling via attenuating DVL1 ubiquitination to achieve the functions. Taken together, the current study revealed an inhibitory role of SPATA2 on EMT and that SPATA2 could be a potential target for therapy of NSCLC. Spermatogenesis associated 2 (SPATA2) inhibited epithelial‐mesenchymal transition leading to impaired metastasis and increased radiosensitivity in non–small cell lung cancer. Mechanistic investigation revealed that SPATA2 binds with CYLD and enhanced CYLD deubiquitinase activity to reduce K63‐linked polyubiquitination of DVL1, which results in DVL1 degradation and subsequently attenuating β‐catenin signaling.
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影响因子：
7.7
作者：
Schlicher, Lisa;Wissler, Manuela;Maurer, Ulrich
通讯作者：
Maurer, Ulrich
影响因子：
16
作者：
Elliott, Paul R.;Leske, Derek;Hrdinka, Matous;Bagola, Katrin;Fiil, Berthe K.;McLaughlin, Stephen H.;Wagstaff, Jane;Volkmar, Norbert;Christianson, John C.;Kessler, Benedikt M.;Freund, Stefan M. V.;Komander, David;Gyrd-Hansen, Mads
通讯作者：
Gyrd-Hansen, Mads
DOI：
10.1006/bbrc.2001.4754
发表时间：
2001-04-27
影响因子：
3.1
作者：
Maurizio, O;Liliana, SM;Carlo, F
通讯作者：
Carlo, F
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
11.4
作者：
Wagner, Sebastian A.;Satpathy, Shankha;Choudhary, Chunaram
通讯作者：
Choudhary, Chunaram