Overexpression of Tetraspanin31 contributes to malignant potential and poor outcomes in gastric cancer.
Overexpression of Tetraspanin31 contributes to malignant potential and poor outcomes in gastric cancer.
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四跨膜蛋白通过与细胞内信号蛋白相互作用的各种蛋白质聚集在许多癌症中具有重要功能。Tetraspanin 31（TSPAN 31）位于多种癌症的12 q14扩增区域，其在胃癌（GC）中的分子功能尚不清楚。我们测试了TSPAN 31是否通过其在GC中的激活或过表达作为促癌基因。我们分析了7个GC细胞系和189个原发性肿瘤，这些肿瘤在2011年至2013年期间在我们医院进行了根治性切除。在3个胃癌细胞系（42.9%）和62个原发性胃癌标本（32.8%）中经常检测到TSPAN 31蛋白的过表达。TSPAN 31的过表达与淋巴管浸润、静脉浸润、更晚期的pT和pN分期以及更高的复发率显著相关。此外，TSPAN 31阳性是预测患者结局较差的独立因素（p = 0.0283，风险比3.97）。TSPAN 31的异位过表达促进了GC细胞的细胞增殖，TSPAN 31的敲低通过PI 3 K-Akt途径抑制了GC细胞的细胞增殖、迁移、侵袭和上皮-间质转化，并以TP 53突变非依赖性方式增加了细胞凋亡。体内分析还显示TSPAN 31的敲低抑制肿瘤进展。此外，TSPAN 31的敲除通过抑制ABCC 2改善了对顺铂的化学敏感性。这些研究结果表明，TSPAN 31通过过表达在肿瘤恶性潜能中起着至关重要的作用，突出了其作为预后因子和GC中潜在治疗靶点的实用性。我们发现Tetraspanin 31（TSPAN 31）在原发性胃癌标本中经常过表达，并与肿瘤进展和不良结局相关。此外，TSPAN 31的敲低抑制细胞增殖、迁移和侵袭，以及改善对顺铂的化疗抗性。
Tetraspanin has important functions in many cancers by aggregating with various proteins that interact with intracellular signaling proteins. The molecular function of Tetraspanin31 (TSPAN31), located in the 12q14 amplified region in various cancers, remains unclear in gastric cancer (GC). We tested whether TSPAN31 acts as a cancer‐promoting gene through its activation or overexpression in GC. We analyzed seven GC cell lines and 189 primary tumors, which were curatively resected in our hospital between 2011 and 2013. Overexpression of the TSPAN31 protein was frequently detected in three GC cell lines (42.9%) and 62 primary GC specimens (32.8%). Overexpression of TSPAN31 was significantly correlated with lymphatic invasion, venous invasion, more advanced pT and pN stages, and a higher recurrence rate. Moreover, TSPAN31 positivity was an independent factor predicting worse patient outcomes (p = 0.0283, hazard ratio 3.97). Ectopic overexpression of TSPAN31 facilitated cell proliferation of GC cells, and knockdown of TSPAN31 inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition of GC cells through the PI3K‐Akt pathway and increased cell apoptosis in a TP53 mutation‐independent manner. In vivo analysis also revealed knockdown of TSPAN31 suppressed tumor progression. In addition, knockdown of TSPAN31 improved chemosensitivity to cisplatin through the suppression of ABCC2. These findings suggest that TSPAN31 plays a crucial role in tumor‐malignant potential through overexpression, highlighting its utility as a prognostic factor and a potential therapeutic target in GC. We showed that Tetraspanin31 (TSPAN31) was frequently overexpressed in primary gastric cancer specimens and related to tumor progression and poor outcomes. Moreover, knockdown of TSPAN31 suppressed cell proliferation, migration, and invasion, as well as improving chemotherapy resistance to cisplatin.
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影响因子：
4.7
作者：
Imamura, Taisuke;Komatsu, Shuhei;Otsuji, Eigo
通讯作者：
Otsuji, Eigo
影响因子：
6.3
作者：
Nakamoto, Taisei;Murayama, Yoko;Hayashi, Norio
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Hayashi, Norio
影响因子：
168.9
作者：
Kang, Yoon-Koo;Boku, Narikazu;Chen, Li-Tzong
通讯作者：
Chen, Li-Tzong
影响因子：
8
作者：
Mischel, PS;Shai, R;Nelson, SF
通讯作者：
Nelson, SF
影响因子：
8.8
作者：
Nishimura, Y.;Komatsu, S.;Ichikawa, D.;Nagata, H.;Hirajima, S.;Takeshita, H.;Kawaguchi, T.;Arita, T.;Konishi, H.;Kashimoto, K.;Shiozaki, A.;Fujiwara, H.;Okamoto, K.;Tsuda, H.;Otsuji, E.
通讯作者：
Otsuji, E.