Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness.
Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness.
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DOI：
10.1186/1471-2407-14-194
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发表时间：
2014-03-15
期刊：
影响因子：
3.8
通讯作者：
Ding SJ
中科院分区：
文献类型：
--
作者：
Jami MS;Hou J;Liu M;Varney ML;Hassan H;Dong J;Geng L;Wang J;Yu F;Huang X;Peng H;Fu K;Li Y;Singh RK;Ding SJ
KIAA 1199是最近发现的一个新基因，在人类癌症中表达上调，生存率低。我们对趋化细胞信号极性的蛋白质组学研究表明，KIAA 1199是一种新的蛋白质靶点，可能参与细胞的趋化性和运动性。在本研究中，我们研究了KIAA 1199表达在乳腺癌生长、运动和侵袭中的功能意义。我们使用含有12个乳腺肿瘤组织核心和12个相应正常组织的TMA载玻片，通过组织微阵列免疫组织化学验证了先前的微阵列观察。我们在MDA-MB-231和HS 578 T细胞中进行了shRNA介导的KIAA 1199敲低，以研究该蛋白在体外细胞增殖、迁移和凋亡中的作用。我们在两组小鼠（n = 5）中研究了KIAA 1199敲低的体内效应。我们进行了SILAC LC-MS/MS为基础的蛋白质组学研究的参与KIAA 1199在乳腺癌。KIAA 1199 mRNA和蛋白在乳腺肿瘤标本和细胞系中显著过表达，与来自大规模微阵列和乳腺癌细胞系和肿瘤研究的非肿瘤性乳腺组织相比。为了更深入地了解KIAA 1199在乳腺癌中的新作用，我们在表达更高水平KIAA 1199的两种乳腺癌细胞系（MDA-MB-231和HS 578 T）中使用shRNA介导的敲低来调节KIAA 1199的表达。KIAA 1199敲低的细胞在体外表现出降低的运动性和细胞增殖。此外，当敲除的细胞被注射到雌性无胸腺裸鼠的乳腺脂肪垫中时，肿瘤发生率和生长显著降低。此外，定量蛋白质组学分析显示，乳腺癌（MDA-MB-231）细胞中KIAA 1199的敲低影响了广泛的细胞功能，包括凋亡，代谢和细胞运动。我们的研究结果表明，KIAA 1199可能在乳腺肿瘤生长和侵袭性中发挥重要作用，并且它可能代表生物标志物开发的新靶点和乳腺癌的新治疗靶点。
KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it may represent a novel target for biomarker development and a novel therapeutic target for breast cancer.
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影响因子：
3.7
作者：
Matsuzaki, Shinji;Tanaka, Fumiaki;Mori, Masaki
通讯作者：
Mori, Masaki
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
7.4
作者：
Hou J;Dong J;Sun L;Geng L;Wang J;Zheng J;Li Y;Bridge J;Hinrichs SH;Ding SJ
通讯作者：
Ding SJ
DOI：
10.1073/pnas.96.14.7992
发表时间：
1999-07-06
影响因子：
11.1
作者：
García-Domingo, D;Leonardo, E;Martínez, C
通讯作者：
Martínez, C