Identification of inositol polyphosphate 4-phosphatase type II as a novel tumor resistance biomarker in human laryngeal cancer HEp-2 cells.
Identification of inositol polyphosphate 4-phosphatase type II as a novel tumor resistance biomarker in human laryngeal cancer HEp-2 cells.
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DOI：
10.4161/cbt.21788
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发表时间：
2012-11
影响因子：
3.6
通讯作者：
Hwang SG
中科院分区：
文献类型：
--
作者：
Kim JS;Yun HS;Um HD;Park JK;Lee KH;Kang CM;Lee SJ;Hwang SG
虽然肿瘤耐药仍然是放射治疗成功的重要障碍，但相关的调节标志物和支持这一现象的详细分子机制尚未很好地定义。在这项研究中，我们通过系统分析喉癌的Unigene文库，确定了肌醇多磷酸4-磷酸酶II(INPP4B)是一个新的放射抗性标记。INPP4B在辐射抵抗的喉癌细胞中高表达，并在不同类型的癌细胞中被放射或抗癌药物诱导。异位INPP4B过表达通过抑制Hep-2细胞的凋亡而增加放射抗性和抗癌耐药性。相反，INPP4B缺失与小干扰RNA一起使Hep-2以及A549和H1299细胞对辐射和抗癌药物诱导的细胞凋亡重新敏感。此外，辐射诱导的INPP4B表达可通过抑制细胞外信号调节激酶(ERK)而被阻断。INPP4B缺失显著减弱辐射诱导的Akt磷酸化增加，表明INPP4B介导的辐射抗性与Akt生存信号有关。综上所述，我们的数据表明，ERK依赖的INPP4B的诱导通过Akt信号触发了肿瘤耐药表型的发展，并确认INPP4B是一个潜在的解决癌细胞辐射抗性的重要靶分子。
Although tumor resistance remains a significant impediment to successful radiotherapy, associated regulatory markers and detailed molecular mechanisms underlying this phenomenon are not well defined. In this study, we identified inositol polyphosphate 4-phosphatase type II (INPP4B) as a novel marker of radioresistance by systematically analyzing Unigene libraries of laryngeal cancer. INPP4B was highly expressed in radioresistant laryngeal cancer cells and was induced by treatment with either radiation or anticancer drugs in various types of cancer cells. Ectopic INPP4B overexpression increased radioresistance and anticancer drug resistance by suppressing apoptosis in HEp-2 cells. Conversely, INPP4B depletion with small interfering RNA resensitized HEp-2 as well as A549 and H1299 cells to radiation- and anticancer drug-induced apoptosis. Furthermore, radiation-induced INPP4B expression was blocked by inhibition of extracellular signal-regulated kinase (ERK). INPP4B depletion significantly attenuated radiation-induced increases in Akt phosphorylation, indicating an association of INPP4B-mediated radioresistance with Akt survival signaling. Taken together, our data suggest that ERK-dependent induction of INPP4B triggers the development of a tumor-resistance phenotype via Akt signaling and identify INPP4B as a potentially important target molecule for resolving the radioresistance of cancer cells.
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影响因子：
11.2
作者：
Das, Amit K.;Sato, Mitsuo;Nirodi, Chaitanya S.
通讯作者：
Nirodi, Chaitanya S.
影响因子：
4.8
作者：
Kim, Jae-Sung;Ryoo, Zae Young;Chun, Jang-Soo
通讯作者：
Chun, Jang-Soo
影响因子：
12.4
作者：
Kim, JS;Park, ZY;Chun, JS
通讯作者：
Chun, JS
影响因子：
4.8
作者：
Kisseleva, MV;Cao, L;Majerus, PW
通讯作者：
Majerus, PW
DOI：
10.1016/s0360-3016(02)03037-7
发表时间：
2002-11-01
影响因子：
7
作者：
Henness, S;Davey, MW;Davey, RA
通讯作者：
Davey, RA