Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer.
Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer.
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DOI：
10.1038/s41598-018-31069-2
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发表时间：
2018-09-04
影响因子：
4.6
通讯作者：
Yaegashi N
中科院分区：
文献类型：
--
作者：
Ishibashi M;Toyoshima M;Zhang X;Hasegawa-Minato J;Shigeta S;Usui T;Kemp CJ;Grandori C;Kitatani K;Yaegashi N
铂类耐药是卵巢癌治疗中最具挑战性的问题之一。高通量功能性siRNA筛选鉴定了具有免疫球蛋白样和EGF样结构域1（TIE-1）的酪氨酸激酶作为赋予细胞顺铂抗性的基因。相反，TIE-1的强制过表达被证实可降低多种卵巢癌细胞系中的顺铂敏感性，并且TIE-1的上调与卵巢癌患者的不良预后和顺铂耐药性相关。在机制上，TIE-1上调由着色性干皮病互补组C（XPC）介导的核苷酸切除修复（NER）系统，从而导致对顺铂诱导的细胞死亡的敏感性降低，而不影响顺铂摄取和排泄。重要的是，通过TIE-1抑制增强治疗功效对DNA加合物型化疗铂试剂具有选择性。因此，TIE-1被认为促进XPC依赖性NER，使卵巢癌细胞对铂产生耐药性。伴随着新的发现，TIE-1可能成为铂类耐药卵巢癌的一个新的治疗靶点。
Platinum resistance is one of the most challenging problems in ovarian cancer treatment. High-throughput functional siRNA screening identified tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) as a gene that confers cells resistant to cisplatin. Conversely enforced over-expression of TIE-1 was validated to decrease cisplatin sensitivity in multiple ovarian cancer cell lines and up-regulation of TIE-1 was correlated with poor prognosis and cisplatin resistance in patients with ovarian cancer. Mechanistically, TIE-1 up-regulates the nucleotide excision repair (NER) system mediated by xeroderma pigmentosum complementation group C (XPC), thereby leading to decreased susceptibility to cisplatin-induced cell death without affecting cisplatin uptake and excretion. Importantly potentiation of therapeutic efficacy by TIE-1 inhibition was selective to DNA-adduct-type chemotherapeutic platinum reagents. Therefore, TIE-1 is suggested to promote XPC-dependent NER, rendering ovarian cancer cells resistant to platinum. Accompanied with novel findings, TIE-1 could represent as a novel therapeutic target for platinum-resistant ovarian cancer.
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DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Du, James X.;Bialkowska, Agnieszka B.;Yang, Vincent W.
通讯作者：
Yang, Vincent W.
DOI：
10.1073/pnas.89.7.3070
发表时间：
1992-04-01
影响因子：
11.1
作者：
GODWIN, AK;MEISTER, A;ANDERSON, ME
通讯作者：
ANDERSON, ME
影响因子：
82.9
作者：
Oishi, Yumiko;Manabe, Ichiro;Nagai, Ryozo
通讯作者：
Nagai, Ryozo
影响因子：
64.8
作者：
Friedberg, EC
通讯作者：
Friedberg, EC