Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.
Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.
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DOI：
10.1038/oncsis.2016.76
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发表时间：
2016-12-12
期刊：
影响因子：
6.2
通讯作者：
Koike, K.
中科院分区：
文献类型：
--
作者：
Tanaka, Y.;Tateishi, K.;Nakatsuka, T.;Kudo, Y.;Takahashi, R.;Miyabayashi, K.;Yamamoto, K.;Asaoka, Y.;Ijichi, H.;Tateishi, R.;Shibahara, J.;Fukayama, M.;Ishizawa, T.;Hasegawa, K.;Kokudo, N.;Koike, K.
Sharpin（Shank 相关 RH 结构域相互作用蛋白，也称为 SIPL1）是一种多功能分子，参与多种生物环境，包括核因子-κB 信号传导激活和肿瘤抑制基因抑制。 Sharpin 在多种类型的癌症中表达上调，包括肝细胞癌 (HCC)，并且与肿瘤进展有关。然而，Sharpin 在肿瘤发生和肿瘤进展中的确切作用仍然很大程度上未知。在这里，我们报告了通过 Sharpin 过度表达导致 HCC 进展的新机制。在我们的研究中，Sharpin 在人类 HCC 组织中表达上调。 Sharpin 表达增加增强肝癌细胞侵袭，而通过 RNA 干扰减少 Sharpin 表达抑制侵袭。微阵列分析发现，Versacan（一种在肿瘤进展和侵袭中起关键作用的硫酸软骨素蛋白多糖）在表达 Sharpin 的稳定细胞中也表达上调。大多数 HCC 组织中 Versican 表达增加，敲低 Versican 大大减弱了肝癌细胞的侵袭。 Sharpin 表达与 Wnt/β-catenin 通路激活协同作用，显着诱导 Versican 转录。此外，Sharpin 过表达细胞在体内具有高致瘤特性。这些结果表明 Sharpin 与 Wnt/β-catenin 通路协同促进 Versican 表达，可能有助于 HCC 的发展。 Sharpin/Versacan 轴可能成为这种目前无法治疗的癌症的一个有吸引力的治疗靶点。
Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-κB signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here we report novel mechanisms of HCC progression through Sharpin overexpression. In our study, Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that Versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in Sharpin-expressing stable cells. Versican expression increased in the majority of HCC tissues and knocking down of Versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of Versican transcription synergistically with Wnt/β-catenin pathway activation. Furthermore, Sharpin-overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes Versican expression synergistically with the Wnt/β-catenin pathway, potentially contributing to HCC development. A Sharpin/Versican axis could be an attractive therapeutic target for this currently untreatable cancer.
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DOI：
10.1111/j.1349-7006.2002.tb01226.x
发表时间：
2002-11
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Ikenoue T;Ijichi H;Kato N;Kanai F;Masaki T;Rengifo W;Okamoto M;Matsumura M;Kawabe T;Shiratori Y;Omata M
通讯作者：
Omata M
影响因子：
5
作者：
Seymour, R. E.;Hasham, M. G.;Sundberg, J. P.
通讯作者：
Sundberg, J. P.
SHARPIN 过表达通过 NF-kappa B/ERK/Akt 信号通路诱导人前列腺癌 LNCaP、DU145 和 PC-3 细胞肿瘤发生
影响因子：
3.4
作者：
Li, Jin;Lai, Yiming;Guo, Zhenghui
通讯作者：
Guo, Zhenghui
影响因子：
4.8
作者：
Domenzain-Reyna, Clelia;Hernandez, Daniel;Bassols, Anna
通讯作者：
Bassols, Anna
影响因子：
64.8
作者：
Ikeda, Fumiyo;Deribe, Yonathan Lissanu;Skanland, Sigrid S.;Stieglitz, Benjamin;Grabbe, Caroline;Franz-Wachtel, Mirita;van Wijk, Sjoerd J. L.;Goswami, Panchali;Nagy, Vanja;Terzic, Janos;Tokunaga, Fuminori;Androulidaki, Ariadne;Nakagawa, Tomoko;Pasparakis, Manolis;Iwai, Kazuhiro;Sundberg, John P.;Schaefer, Liliana;Rittinger, Katrin;Macek, Boris;Dikic, Ivan
通讯作者：
Dikic, Ivan