RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:JAML overexpressed in colorectal cancer promotes tumour proliferation by activating the PI3K-AKT-mTOR signalling pathway.
JAML overexpressed in colorectal cancer promotes tumour proliferation by activating the PI3K-AKT-mTOR signalling pathway.
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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。
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.
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