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阳离子氨基酸转运体 PQLC2 是胃癌的潜在治疗靶点。

Cationic amino acid transporter PQLC2 is a potential therapeutic target in gastric cancer.

机构信息

Biomedical Translational Research Center, KRIBB, Daejeon, Korea.

Department of Pathology and Medical Science, Chungnam National University College of Medicine, Daejeon, Korea.

出版信息

Cancer Sci. 2019 Apr;110(4):1453-1463. doi: 10.1111/cas.13966. Epub 2019 Mar 19.

Abstract

Tumor cells overexpress amino acid transporters to meet the increased demand for amino acids. PQ loop repeat-containing (PQLC)2 is a cationic amino acid transporter that might be involved in cancer progression. Here, we show that upregulation of PQLC2 is critical to gastric cancer (GC) development in vitro and in vivo. Both PQLC2 mRNA and protein were overexpressed in GC tissues, especially of the diffuse type. Overexpression of PQLC2 promoted cell growth, anchorage independence, and tumor formation in nude mice. This was due to activation of MEK/ERK1/2 and PI3K/AKT signaling. Conversely, PQLC2 knockdown caused growth arrest and cell death of cancer cells and suppressed tumor growth in a mouse xenograft model. These results suggest that targeting PQLC2 is an effective strategy for GC treatment.

摘要

肿瘤细胞过度表达氨基酸转运体以满足对氨基酸的需求增加。含有 PQ 环重复序列的(PQLC)2 是一种阳离子氨基酸转运体,可能参与癌症的进展。在这里,我们表明 PQLC2 的上调对于体外和体内胃癌(GC)的发展至关重要。PQLC2 的 mRNA 和蛋白在 GC 组织中均过度表达,特别是弥漫型。PQLC2 的过表达促进了裸鼠中的细胞生长、锚定独立性和肿瘤形成。这是由于 MEK/ERK1/2 和 PI3K/AKT 信号的激活。相反,PQLC2 的敲低导致癌细胞的生长停滞和细胞死亡,并抑制了小鼠异种移植模型中的肿瘤生长。这些结果表明,靶向 PQLC2 是治疗 GC 的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06c/6447956/a829fc91c974/CAS-110-1453-g001.jpg

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