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结直肠癌中 JAML 过表达通过激活 PI3K-AKT-mTOR 信号通路促进肿瘤增殖

英文原题:JAML overexpressed in colorectal cancer promotes tumour proliferation by activating the PI3K-AKT-mTOR signalling pathway.

查看英文原题

JAML overexpressed in colorectal cancer promotes tumour proliferation by activating the PI3K-AKT-mTOR signalling pathway.

PubMed 2024/10/18(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

JAML在结直肠癌(CRC)中的表达及生物学功能尚不清楚。收集50例CRC的石蜡组织样本,以检测JAML的表达。在CRC细胞中过表达或敲低JAML,以评估体外和体内的增殖、迁移和侵袭能力。应用Western-blot及其他方法探讨其机制。研究显示,50%(25/50)的CRC患者癌组织中JAML高表达,并与较高的TNM分期相关(p < 0.05)。JAML高表达组患者的总生存期较JAML低表达组更差(p = 0.0362,HR = 0.4295,95% CI为0.1908-0.9667)。JAML高表达组的TIL(肿瘤浸润淋巴细胞)(TILs)低于JAML低表达组(p < 0.05)。JAML过表达通过激活PI3K-AKT-mTOR信号通路,在体外和体内均促进CRC的增殖、迁移和侵袭。在JAML高表达肿瘤组织中,通过降低CCL20和CXCL9/10/11等趋化因子,TILs减少。

我们的研究确定了JAML——一种在CRC组织中特异性高表达、可能理想的靶点,其促进肿瘤增殖、损害T淋巴细胞浸润,为CRC患者提供了一种有前景的治疗策略。

展开英文摘要原文

The expression and biological function of junctional adhesion molecule-like protein (JAML) in colorectal cancer (CRC) remain unclear. Paraffin tissue samples from 50 cases of CRC were collected to determine the expression of JAML. JAML was overexpressed or knock-down in CRC cells to evaluated the proliferation, migration and invasion in vitro and in vivo. Western-blot and others were applied to explore the mechanisms. The study showed that JAML was highly expressed within cancer tissues in 50% (25/50) of patients with CRC, and was correlated with higher TNM stage (p < 0.

05). Patients of JAML -high group had poorer overall survival compared to JAML -low group (p = 0. 0362, HR = 0. 4295, 95% CI of 0. 1908-0. 9667). The tumour infiltrating lymphocytes (TILs) was lower in the JAML -high group than in the JAML -low group (p < 0. 05). Overexpression of JAML promoted the proliferation, migration, and invasion of CRC by activating the PI3K-AKT-mTOR signalling pathway both in vitro and in vivo. TILs were reduced in JAML -high tumour tissues by decreasing chemokines such as CCL20 and CXCL9/10/11.

Our study identified JAML, a potentially ideal target that is specifically highly expressed in CRC tissues, which promoted tumour proliferation, impaired T-lymphocytes infiltration, provided a promising therapeutic strategy for patients with CRC.

论文信息

作者
Fang Y、Liu Y、Dong Z、Zhao X、Zhang M、Zheng Y、Yang C、Wang Y
第一作者单位
Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, Shandong, People's Republic of China.China
通讯作者单位
Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, Shandong, People's Republic of China. smli1980@163.com.China
期刊
Scientific reports2024 Oct 18
原文标识
PubMed 39424882 · DOI 10.1038/s41598-024-75180-z