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CEACAM6 通过增强前列腺癌细胞的增殖、迁移和抑制细胞凋亡来促进肺转移。

CEACAM6 Promotes Lung Metastasis via Enhancing Proliferation, Migration and Suppressing Apoptosis of Prostate Cancer Cells.

发表日期:2024
作者: Alireza Saraji, Katharina Wulf, Janine Stegmann-Frehse, Duan Kang, Anne Offermann, Gevorg Shaghoyan, Danny Jonigk, Mark Philipp Kühnel, Sven Perner, Jutta Kirfel, Verena Sailer
来源: Cellular & Molecular Immunology

摘要:

转移性前列腺癌(mPCa)导致高发病率和死亡率。内脏转移尤其与生存期缩短有关。我们的目的是揭示 mPCa 肺部扩散的分子机制。我们对 PCa 肺转移进行了全面的转录组分析,然后对候选基因进行了功能验证。利用 NanoString 技术对从 PCa 肺转移瘤的福尔马林固定石蜡包埋 (FFPE) 组织中提取的 mRNA 进行数字基因表达分析。比较了原发性PCa和PCa肺转移瘤的基因表达数据,并使用几种公开的生物信息学分析工具对数据进行注释和验证。在PCa肺转移瘤中,234个基因显着上调,78个基因显着下调。与原发性 PCa 相比受到调节。癌胚抗原相关细胞粘附分子6(CEACAM6)被确定为适合进一步功能验证的候选基因。 CEACAM6 作为一种细胞粘附分子,与促进结直肠癌或胃癌等多种实体瘤的转移性疾病有关。我们发现 PC-3 和 LNCaP 细胞中 CEACAM6 的 siRNA 敲低导致细胞活力和迁移降低以及细胞凋亡增强。综合转录组分析确定了几个可能促进转移扩散至肺部的感兴趣基因。功能验证表明,CEACAM6 可能通过增强 PC-3 和 PC-3 中的增殖、迁移和抑制细胞凋亡,在促进 PCa 患者肺部转移扩散中发挥重要作用。 LNCaP 细胞。 CEACAM6 可能会成为预防转移性疾病的有吸引力的治疗靶点。版权所有 © 2024,国际抗癌研究所(George J. Delinasios 博士),保留所有权利。
Metastatic prostate cancer (mPCa) results in high morbidity and mortality. Visceral metastases in particular are associated with a shortened survival. Our aim was to unravel the molecular mechanisms that underly pulmonary spread in mPCa.We performed a comprehensive transcriptomic analysis of PCa lung metastases, followed by functional validation of candidate genes. Digital gene expression analysis utilizing the NanoString technology was performed on mRNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissue from PCa lung metastases. The gene expression data from primary PCa and PCa lung metastases were compared, and several publicly available bioinformatic analysis tools were used to annotate and validate the data.In PCa lung metastases, 234 genes were considerably up-regulated, and 78 genes were significantly down-regulated when compared to primary PCa. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) was identified as suitable candidate gene for further functional validation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumors, such as colorectal or gastric cancer. We showed that siRNA knockdown of CEACAM6 in PC-3 and LNCaP cells resulted in decreased cell viability and migration as well as enhanced apoptosis. Comprehensive transcriptomic analyses identified several genes of interest that might promote metastatic spread to the lung.Functional validation revealed that CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation, migration and suppressing apoptosis in PC-3 and LNCaP cells. CEACAM6 might pose an attractive therapeutic target to prevent metastatic disease.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.