The germline factor DDX4 contributes to the chemoresistance of small cell lung cancer cells.
The germline factor DDX4 contributes to the chemoresistance of small cell lung cancer cells.
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DOI：
10.1038/s42003-023-04444-7
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发表时间：
2023-01-18
影响因子：
5.9
通讯作者：
Yajima, Mamiko
中科院分区：
文献类型：
--
作者：
Noyes, Christopher;Kitajima, Shunsuke;Li, Fengkai;Suita, Yusuke;Miriyala, Saradha;Isaac, Shakson;Ahsan, Nagib;Knelson, Erik;Vajdi, Amir;Tani, Tetsuo;Thai, Tran C.;Xu, Derek;Murai, Junko;Tapinos, Nikos;Takahashi, Chiaki;Barbie, David A.;Yajima, Mamiko
人类癌症经常重新表达种系因子，但它们在肿瘤发生和癌症进展中的机制作用仍然未知。在这里，我们证明 DEAD-box 解旋酶 4 (DDX4) 是一种在所有多细胞生物中保守的种系因子和 RNA 解旋酶，有助于增加小细胞肺癌 (SCLC) 细胞的细胞运动性和顺铂介导的耐药性。蛋白质组学分析表明，DDX4 表达上调与 DNA 修复和免疫/炎症反应相关的蛋白质。与细胞系中的这些趋势一致，DDX4 的消耗会损害体内肿瘤的发展，而其过度表达甚至在裸鼠顺铂治疗后也会增强肿瘤的生长。此外，SCLC 患者中相对较高的 DDX4 表达与生存率降低相关，并显示免疫/炎症反应标志物表达增加。综上所述，我们认为 DDX4 通过增加 DNA 损伤和免疫反应途径来增加 SCLC 细胞的存活率，特别是在顺铂治疗等挑战性条件下。 DDX4 是一种保守的种系因子和 RNA 解旋酶，通过调节 DNA 损伤和免疫反应途径来提高小细胞肺癌细胞的存活率，并有助于顺铂介导的耐药性。
Human cancers often re-express germline factors, yet their mechanistic role in oncogenesis and cancer progression remains unknown. Here we demonstrate that DEAD-box helicase 4 (DDX4), a germline factor and RNA helicase conserved in all multicellular organisms, contributes to increased cell motility and cisplatin-mediated drug resistance in small cell lung cancer (SCLC) cells. Proteomic analysis suggests that DDX4 expression upregulates proteins related to DNA repair and immune/inflammatory response. Consistent with these trends in cell lines, DDX4 depletion compromised in vivo tumor development while its overexpression enhanced tumor growth even after cisplatin treatment in nude mice. Further, the relatively higher DDX4 expression in SCLC patients correlates with decreased survival and shows increased expression of immune/inflammatory response markers. Taken together, we propose that DDX4 increases SCLC cell survival, by increasing the DNA damage and immune response pathways, especially under challenging conditions such as cisplatin treatment. DDX4, a conserved germline factor and RNA helicase, increases small cell lung cancer cell survival by regulating DNA damage and immune response pathways and contributes to cisplatin-mediated drug resistance.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
64.5
作者：
HAY, B;JAN, LY;JAN, YN
通讯作者：
JAN, YN
DOI：
10.1016/j.bbrc.2014.03.144
发表时间：
2014-05-02
影响因子：
3.1
作者：
Kim, Ki Hyung;Kang, Yun-Jeong;Cha, Hee-Jae
通讯作者：
Cha, Hee-Jae
影响因子：
64.8
作者：
Hondele, Maria;Sachdev, Ruchika;Weis, Karsten
通讯作者：
Weis, Karsten
影响因子：
64.8
作者：
LASKO, PF;ASHBURNER, M
通讯作者：
ASHBURNER, M