Inhibition of p600 expression suppresses both invasiveness and anoikis resistance of gastric cancer.
Inhibition of p600 expression suppresses both invasiveness and anoikis resistance of gastric cancer.
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DOI：
10.1245/s10434-010-1523-0
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发表时间：
2011-07
影响因子：
3.7
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Sakai H;Ohuchida K;Mizumoto K;Cui L;Nakata K;Toma H;Nagai E;Tanaka M
进展期胃癌常常转移到远处器官和腹膜，导致预后不良。侵袭性和对锚定非依赖性细胞死亡（失巢凋亡）的抵抗是转移过程中的重要因素。最近从宫颈癌细胞系中鉴定出p600（600-kDa蛋白），其在抗失巢凋亡和细胞迁移中起作用。在这项研究中，我们研究了p600是否参与胃癌的进展。我们使用正常胃粘膜细胞和癌细胞激光显微切割42胃癌和他们的正常同行，并比较其p600 mRNA的表达水平与定量逆转录聚合酶链反应。我们用siRNA抑制两种胃癌细胞系中p600的表达，并在体外和体内检测其对侵袭力和抗失巢凋亡的影响。p600 mRNA在胃癌细胞中的表达显著高于正常胃粘膜细胞（P = 0.027）。侵袭实验显示，抑制p600可显著降低细胞的侵袭能力（P < 0.01）。体外实验表明，抑制p600可显著降低非贴壁条件下的细胞存活率和集落形成能力（P < 0.05）。体内实验也表明，瞬时抑制p600可显著抑制腹腔播散性肿瘤的形成（P < 0.001）。我们的研究结果表明，p600参与胃癌的进展，并有可能成为胃癌治疗的新的分子靶点。
Advanced gastric cancers often metastasize to distant organs and the peritoneum, leading to a poor prognosis. Both invasiveness and resistance to anchorage-independent cell death (anoikis) are important factors in the process of metastasis. p600 (600-kDa protein), recently identified from a cervical cancer cell line, plays a role in both anoikis resistance and cell migration. In this study, we examined whether p600 is involved in the progression of gastric cancer. We used both normal gastric mucosal cells and cancer cells laser-microdissected from 42 gastric cancers and their normal counterparts, and compared their p600 mRNA expression levels with quantitative reverse transcriptase–polymerase chain reaction. We inhibited p600 expression in two gastric cancer cell lines with siRNA and examined its effect on the invasiveness and anoikis resistance both in vitro and in vivo. Expression of p600 mRNA was significantly higher in gastric cancer cells than in normal mucosal cells (P = 0.027). The invasion assay revealed that invasiveness was significantly reduced by inhibition of p600 (P < 0.01). In vitro experiments revealed that cell viability and colony-formation capacity under anchorage-independent conditions were significantly reduced by inhibition of p600 (P < 0.05). In vivo experiments also showed that the establishment of intraperitoneal disseminated tumors was significantly suppressed by transient inhibition of p600 (P < 0.001). Our results strongly suggest that p600 is involved in gastric cancer progression, and has a potential to be a new molecular target for gastric cancer therapy.
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DOI：
10.1073/pnas.0505337102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Huh, KW;DeMasi, J;Münger, K
通讯作者：
Münger, K
影响因子：
37.3
作者：
Vasseur, Sophie;Malicet, Cedric;Iovanna, Juan L.
通讯作者：
Iovanna, Juan L.
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
9.7
作者：
Zhang, L;Mizumoto, K;Tanaka, M
通讯作者：
Tanaka, M
DOI：
10.1073/pnas.0507458102
发表时间：
2005-10-18
影响因子：
11.1
作者：
Nakatani, Y;Konishi, H;Herlitz, AM
通讯作者：
Herlitz, AM