Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer.
Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer.
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DOI：
10.18632/oncotarget.9951
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Mandai M
中科院分区：
文献类型：
--
作者：
Yamanoi K;Matsumura N;Murphy SK;Baba T;Abiko K;Hamanishi J;Yamaguchi K;Koshiyama M;Konishi I;Mandai M
失巢耐药是癌症的一个标志，并与恶性表型有关，包括化疗耐药、肿瘤干细胞样表型和播散。这项研究的目的是利用功能基因组学筛查来确定导致卵巢癌失巢耐药的关键因素。将81000个针对15000个基因的shRNA文库导入OVCA420细胞，软琼脂培养和菌落筛选。我们发现针对ABHD2、ELAC2和CyB5R3的shRNAs可引起可重复的失巢诱导抗性。根据癌症基因组图谱的数据，这三个基因在许多浆液性卵巢癌中都是缺失的。抑制OVCA420细胞中的ABHD2可增加p38和ERK的磷酸化、铂耐药和侧群细胞(分别为P<；0.01)。相反，ABHD2的过表达降低了OVCA420和SKOV3细胞对失巢凋亡的抵抗力(p<；0.05)以及磷酸化p38和ERK的数量。在临床浆液性卵巢癌标本中，ABHD2的低表达与铂类耐药和预后不良有关(p<；0.05)。综上所述，我们通过功能基因组学筛选发现了三个与卵巢癌失巢耐药相关的新基因。抑制ABHD2可能会促进浆液性卵巢癌患者的恶性表型和不良预后。
Anoikis resistance is a hallmark of cancer, and relates to malignant phenotypes, including chemoresistance, cancer stem like phenotypes and dissemination. The aim of this study was to identify key factors contributing to anoikis resistance in ovarian cancer using a functional genomics screen. A library of 81 000 shRNAs targeting 15 000 genes was transduced into OVCA420 cells, followed by incubation in soft agar and colony selection. We found shRNAs directed to ABHD2, ELAC2 and CYB5R3 caused reproducible anoikis resistance. These three genes are deleted in many serous ovarian cancers according to The Cancer Genome Atlas data. Suppression of ABHD2 in OVCA420 cells increased phosphorylated p38 and ERK, platinum resistance, and side population cells (p<0.01, respectively). Conversely, overexpression of ABHD2 decreased resistance to anoikis (p<0.05) and the amount of phosphorylated p38 and ERK in OVCA420 and SKOV3 cells. In clinical serous ovarian cancer specimens, low expression of ABHD2 was associated with platinum resistance and poor prognosis (p<0.05, respectively). In conclusion, we found three novel genes relevant to anoikis resistance in ovarian cancer using a functional genomics screen. Suppression of ABHD2 may promote a malignant phenotype and poor prognosis for women with serous 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：
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影响因子：
3.7
作者：
Drury LJ;Wendt MK;Dwinell MB
通讯作者：
Dwinell MB
DOI：
10.1158/1541-7786.mcr-13-0638
发表时间：
2014-05
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Han C;Zhao R;Liu X;Srivastava A;Gong L;Mao H;Qu M;Zhao W;Yu J;Wang QE
通讯作者：
Wang QE
影响因子：
9
作者：
通讯作者：
--
影响因子：
4.7
作者：
Lum, Elena;Vigliotti, Michele;Lucito, Robert
通讯作者：
Lucito, Robert