p38γ Activation and BGP (Biliary Glycoprotein) Induction in Primates at Risk for Inflammatory Bowel Disease and Colorectal Cancer-A Comparative Study with Humans.
p38γ Activation and BGP (Biliary Glycoprotein) Induction in Primates at Risk for Inflammatory Bowel Disease and Colorectal Cancer-A Comparative Study with Humans.
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DOI：
10.3390/vaccines8040720
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发表时间：
2020-12-02
期刊：
影响因子：
7.8
通讯作者：
Tobi M
中科院分区：
文献类型：
--
作者：
Talwar H;McVicker B;Tobi M
结直肠癌(CRC)是一种常见的癌症相关死亡原因，其主要原因是结直肠癌肝转移(CRLM)。靶向机制的确定仍在继续，并包括对炎症途径的作用的调查。有趣的是，MAPK在结直肠癌患者中异常表达，但激活状态尚未确定。本研究评估了结直肠癌患者、癌细胞、棉铃虫和普通绒猴组织中p38γ的激活情况。灵长类动物的世界是一个被忽视的资源，因为易患结肠炎的CTT通常容易发生肝转移，而CM发展为结肠炎，但不是结直肠癌。结果表明，结直肠癌患者p38γ蛋白和磷酸化水平明显高于正常对照组和结直肠癌。此外，p38γ的磷酸化在人结直肠癌细胞和肝母细胞瘤细胞中显著升高，而在CM结肠细胞中不明显。此外，p38γ磷酸化的结直肠癌患者可诱导产生癌胚抗原和胆汁糖蛋白。抑制p38MAPK对结直肠癌细胞生长有明显抑制作用，但对细胞凋亡和骨钙素水平无明显影响。总体而言，p38γ在结直肠癌的发生过程中被激活，在人类的CRLM过程中可能涉及CEA抗原，但在很少发生CRLM的CTT或CM中不涉及CEA抗原。
Colorectal cancer (CRC) is a common cause of cancer-related deaths largely due to CRC liver metastasis (CRLM). Identification of targetable mechanisms continues and includes investigations into the role of inflammatory pathways. Of interest, MAPK is aberrantly expressed in CRC patients, yet the activation status is not defined. The present study assessed p38γ activation in CRC patients, cancer cells, and tissues of cotton top tamarin (CTT) and common marmoset (CM). The primate world is an overlooked resource as colitis-CRC-prone CTT are usually inure to liver metastasis while CM develop colitis but not CRC. The results demonstrate that p38γ protein and phosphorylation levels are significantly increased in CRC patients compared to normal subjects and CTT. Furthermore, p38γ phosphorylation is significantly elevated in human CRC cells and hepatoblastoma cells but not in CM colon. Additionally, carcinoembryonic antigen (CEA) and biliary glycoprotein (BGP) are induced in the CRC patients that showed p38γ phosphorylation. Inhibition of p38 MAPK in CRC cells showed a significant decline in cell growth with no effect on apoptosis or BGP level. Overall, p38γ is activated in CRC tumorigenesis and likely involves CEA antigens during CRLM in humans but not in the CTT or CM, that rarely develop CRLM.
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影响因子：
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作者：
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影响因子：
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11.2
作者：
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通讯作者：
Cuenda, Ana
影响因子：
5.5
作者：
FINERTY, S;MACKETT, M;MORGAN, AJ
通讯作者：
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