Oleic Acid and Insulin as Key Characteristics of T2D Promote Colorectal Cancer Deterioration in Xenograft Mice Revealed by Functional Metabolomics.
Oleic Acid and Insulin as Key Characteristics of T2D Promote Colorectal Cancer Deterioration in Xenograft Mice Revealed by Functional Metabolomics.
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功能代谢组学揭示，油酸和胰岛素是 T2D 的关键特征，可促进异种移植小鼠的结直肠癌恶化
DOI：
10.3389/fonc.2021.685059
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Zhang Y;Wang D;Lv B;Hou X;Liu Q;Liao C;Xu R;Zhang Y;Xu F;Zhang P
结直肠癌（CRC）是世界范围内最常见的癌症之一，死亡率高。2型糖尿病（T2 D）是结直肠癌的危险因素之一，可促进结直肠癌的恶化，但其机制尚不清楚。本研究旨在从小分子代谢的角度揭示结直肠癌与2型糖尿病的关系。首先，通过检索现有的代谢组学出版物获得CRC和T2 D中常见失调代谢物的列表。在这些代谢产物中，发现油酸（OA）能够促进结肠癌细胞HCT 116的增殖和迁移。进一步的实验证明，胰岛素可以显著加强这种促进作用，并与OA表现出协同作用。机制研究发现OA和胰岛素通过细胞外信号调节激酶（ERK）1/2/c-Myc/cyclin D1途径协同作用。此外，ERK 1/2抑制剂SCH 772984和细胞周期蛋白依赖性激酶（CDK）4/6抑制剂palbociclib联合使用在体内显示出显著的肿瘤生长抑制作用。总之，目前的研究发现，OA在CRC的发展中起着重要的作用，通过使用功能代谢组学方法。更重要的是，胰岛素和OA被证实通过ERK 1/2/c-Myc/cyclin D1通路在体外和体内协同促进CRC的恶化。我们的研究结果可能有助于阐明T2 D人群中的CRC治疗。
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high mortality worldwide. Type 2 diabetes mellitus (T2D), known as a risk factor of CRC, can promote the deterioration of CRC, but the underlying mechanism is elusive. In this study, we aimed to reveal the relationship between CRC and T2D from the perspective of small-molecule metabolism. First, a list of common dysregulated metabolites in CRC and T2D was obtained by retrieving existing metabolomics publications. Among these metabolites, oleic acid (OA) was found to be able to promote the proliferation and migration of colon carcinoma cell HCT116. Further experiments proved that insulin could significantly strengthen this promotion and showed a synergistic effect with OA. Mechanism study found that OA and insulin acted synergistically through the extracellular signal-regulated kinase (ERK)1/2/c-Myc/cyclin D1 pathway. In addition, the combination of ERK1/2 inhibitor SCH772984 and cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib showed a remarkable inhibitory effect on tumor growth in vivo. Taken together, the current study found that OA plays an important role in CRC development by using a functional metabolomics approach. More importantly, insulin and OA were confirmed to synergistically promote the deterioration of CRC in vitro and in vivo via ERK1/2/c-Myc/cyclin D1 pathway. Our findings may shed light on CRC treatment among the T2D population.
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影响因子：
5.6
作者：
Liotti, Antonietta;Cosimato, Vincenzo;Ulianich, Luca
通讯作者：
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影响因子：
6.6
作者：
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影响因子：
4.8
作者：
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通讯作者：
Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer
DOI：
10.1016/j.bpg.2017.09.012
发表时间：
2017-10-01
影响因子：
3.2
作者：
Fagunwa, Ifewumi O.;Loughrey, Maurice B.;Coleman, Helen G.
通讯作者：
Coleman, Helen G.
影响因子：
19
作者：
Kang S;Tsai LT;Rosen ED
通讯作者：
Rosen ED