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PRKAR1A 的双重作用:作为癌细胞和癌源性干细胞潜在抗癌靶点。

Dualistic Effects of PRKAR1A as a Potential Anticancer Target in Cancer Cells and Cancer-Derived Stem Cells.

机构信息

Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Republic of Korea.

Department of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Mar 1;25(5):2876. doi: 10.3390/ijms25052876.

Abstract

The integration of innovative medical technologies and interdisciplinary collaboration could improve the treatment of cancer, a globally prevalent and often deadly disease. Despite recent advancements, current cancer therapies fail to specifically address recurrence and target cancer stem cells (CSCs), which contribute to relapse. In this study, we utilized three types of cancer cells, from which three types of CSCs were further derived, to conduct a proteomic analysis. Additionally, shared cell surface biomarkers were identified as potential targets for a comprehensive treatment strategy. The selected biomarkers were evaluated through short hairpin RNA treatment, which revealed contrasting functions in cancer cells and CSCs. Knockdown of the identified proteins revealed that they regulate the epithelial-mesenchymal transition (EMT) and stemness via the ERK signaling pathway. Resistance to anticancer agents was consequently reduced, ultimately enhancing the overall anticancer effects of the treatment. Additionally, the significance of these biomarkers in clinical patient outcomes was confirmed using bioinformatics. Our study suggests a novel cancer treatment strategy that addresses the limitations of current anticancer therapies.

摘要

创新的医疗技术的整合和跨学科的合作可以改善癌症的治疗,癌症是一种全球性的、常见的、往往是致命的疾病。尽管最近取得了进展,但目前的癌症疗法未能专门解决复发和针对癌症干细胞(CSC)的问题,而 CSC 是导致癌症复发的原因之一。在这项研究中,我们使用了三种癌细胞,进一步从中衍生出三种 CSC,进行了蛋白质组学分析。此外,还确定了共享的细胞表面生物标志物作为综合治疗策略的潜在靶点。通过短发夹 RNA 处理评估了选定的生物标志物,结果表明它们在癌细胞和 CSC 中具有不同的功能。敲除鉴定出的蛋白质表明,它们通过 ERK 信号通路调节上皮-间充质转化(EMT)和干性。因此,抗癌药物的耐药性降低,最终增强了治疗的整体抗癌效果。此外,还使用生物信息学证实了这些生物标志物在临床患者预后中的重要性。我们的研究提出了一种新的癌症治疗策略,解决了当前抗癌疗法的局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8696/10932193/f3dae0f363f8/ijms-25-02876-g001.jpg

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