CEACAM6 facilitates gastric cancer progression through upregulating SLC27A2.

IF 4.8 3区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Cancer gene therapy Pub Date : 2024-11-19 DOI:10.1038/s41417-024-00846-9
Xiaqiong Mao, Tongtai Liu, Shunying Yu, Yuqi Wei, Chunli Zhou, Xiaoyi Kuai
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引用次数: 0

Abstract

Gastric cancer (GC) is one of the most lethal cancers. However, the underlying mechanisms are not yet fully understood. Here, we investigated the role of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in tumor initiation and progression in GC and proposed therapeutic strategies for CEACAM6-positive patients. In this article, we found that CEACAM6 overexpression promoted GC initiation and progression by overactivating FAO. CEACAM6 promotes SLC27A2 expression, contributing to enhanced fatty acid incorporation. CEACAM6 interacts with both SLC27A2 and USP29, facilitating the deubiquitination of USP29 on SLC27A2. Pharmacological inhibition of SLC27A2 attenuates the tumor-initiating ability of GC. Taken together, CEACAM6 overexpression facilitates GC progression by upregulating fatty acid uptake through SLC27A2, thereby contributing to FAO. Genetic ablation of SLC27A2 is a promising therapeutic strategy for patients with CEACAM6-positive GC.

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CEACAM6 通过上调 SLC27A2 促进胃癌进展。
胃癌(GC)是致死率最高的癌症之一。然而,其潜在机制尚未完全明了。在此,我们研究了癌胚抗原相关细胞粘附分子6(CEACAM6)在胃癌肿瘤发生和发展中的作用,并提出了针对CEACAM6阳性患者的治疗策略。在这篇文章中,我们发现 CEACAM6 的过表达通过过度激活 FAO 促进了 GC 的发生和进展。CEACAM6 可促进 SLC27A2 的表达,从而增强脂肪酸的结合。CEACAM6 与 SLC27A2 和 USP29 相互作用,促进了 USP29 在 SLC27A2 上的去泛素化。药理抑制 SLC27A2 可减轻 GC 的肿瘤诱发能力。综上所述,CEACAM6 的过表达通过上调 SLC27A2 对脂肪酸的摄取促进了 GC 的进展,从而导致 FAO。对 CEACAM6 阳性的 GC 患者来说,基因消融 SLC27A2 是一种很有前景的治疗策略。
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来源期刊
Cancer gene therapy
Cancer gene therapy 医学-生物工程与应用微生物
CiteScore
10.20
自引率
0.00%
发文量
150
审稿时长
4-8 weeks
期刊介绍: Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.
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