PEA15 promotes liver metastasis of colorectal cancer by upregulating the ERK/MAPK signaling pathway.
PEA15 promotes liver metastasis of colorectal cancer by upregulating the ERK/MAPK signaling pathway.
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PEA15通过上调ERK/MAPK信号通路促进结直肠癌肝转移
DOI：
10.3892/or.2018.6825
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发表时间：
2019-01
期刊：
影响因子：
4.2
通讯作者：
Yan C
中科院分区：
文献类型：
--
作者：
Tang B;Liang W;Liao Y;Li Z;Wang Y;Yan C
肝转移是结直肠癌患者死亡的主要原因之一，虽然近期治疗有所改善，但患者的长期生存率并未明显改善。在本研究中，我们利用免疫组织化学方法确定星形胶质细胞15 kDa富集磷蛋白（PEA15）在结直肠癌组织和肝转移癌组织中高表达。与非转移性患者相比，它在转移性结直肠癌患者中也高表达。通过结直肠癌肝转移患者的临床病理数据发现，PEA15的高表达与结直肠癌患者的TNM分期、肝转移及不良预后呈正相关。通过共聚焦免疫荧光显微镜、蛋白质印迹和细胞增殖、迁移和侵袭实验，我们还确定PEA15可以在体外和体内促进癌细胞增殖、上皮间质转化（EMT）和体外癌症干细胞的特征，从而促进侵袭和迁移的能力。此外，我们发现PEA15在异种移植肿瘤转移模型中促进结直肠癌细胞的肝转移。此外，关于机制，我们通过基因芯片分析确定PEA15上调结直肠癌细胞中的ERK/MAPK信号通路。因此，我们得出结论，PEA15可能是结直肠癌治疗肝转移的潜在生物标志物。总的来说，PEA15通过ERK/MAPK信号通路促进结直肠癌肝转移的发展。
Liver metastasis is one of the major causes of death in patients with colorectal cancer, and although treatment has improved recently, the long-term survival rate of patients has not improved significantly. In the present study, we used immunohistochemistry to determine that phosphoprotein enriched in astrocytes-15 kDa (PEA15) was highly expressed in colorectal cancer tissues and liver metastatic cancer tissues. It was also highly expressed in metastatic colorectal cancer patients compared to non-metastatic patients. Through clinicopathological data of patients with liver metastasis of colorectal cancer, we found that high expression of PEA15 was positively correlated with TNM staging, liver metastasis and poor prognosis of colorectal cancer patients. Using confocal immunofluorescence microscopy, western blotting and cell proliferation, migration and invasion assays, we also determined that PEA15 could promote cancer cell proliferation in vitro and in vivo, epithelial mesenchymal transition (EMT) and the characteristics of cancer stem cells in vitro, thus promoting the abilities of invasion and migration. In addition, we revealed that PEA15 promoted the liver metastasis of colorectal cancer cells in a xenograft tumor metastasis model. In addition, concerning the mechanism, we used gene chip analysis to determine that PEA15 upregulated the ERK/MAPK signaling pathway in colorectal cancer cells. Therefore, we concluded that PEA15 may be a potential biomarker for liver metastasis of colorectal cancer therapy. Collectively, PEA15 promoted the development of liver metastasis of colorectal cancer through the ERK/MAPK signaling pathway.
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影响因子：
11.2
作者：
Bartholomeusz C;Rosen D;Wei C;Kazansky A;Yamasaki F;Takahashi T;Itamochi H;Kondo S;Liu J;Ueno NT
通讯作者：
Ueno NT
影响因子：
16.1
作者：
Li, Feng;Mahato, Ram I.
通讯作者：
Mahato, Ram I.
影响因子：
9
作者：
Quintavalle C;Hindupur SK;Quagliata L;Pallante P;Nigro C;Condorelli G;Andersen JB;Tagscherer KE;Roth W;Beguinot F;Heim MH;Ng CKY;Piscuoglio S;Matter MS
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Matter MS
PED/PEA-15与67 KD层粘连蛋白受体相互作用，并调节细胞粘附，迁移，增殖和凋亡。
影响因子：
5.3
作者：
Formisano P;Ragno P;Pesapane A;Alfano D;Alberobello AT;Rea VE;Giusto R;Rossi FW;Beguinot F;Rossi G;Montuori N
通讯作者：
Montuori N
PEA-15在丝氨酸104和丝氨酸116上均未磷酸化可通过阻断β-catenin抑制卵巢癌细胞的肿瘤性和进展。
影响因子：
6.2
作者：
Lee, J.;Bartholomeusz, C.;Krishnamurthy, S.;Liu, P.;Saso, H.;LaFortune, T. A.;Hortobagyi, G. N.;Ueno, N. T.
通讯作者：
Ueno, N. T.