PO.CL01.23 · 临床研究
KRT10在癌症脑转移中的作用
The role of KRT10 in cancer brain metastasis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
KRT10是一种角蛋白家族蛋白，调控上皮结构和细胞分化。虽然KRT10在癌症转移中的作用此前已有报道，但其参与机制仍不明确。在本研究中，我们应用了一种整合的多组学策略——包括空间转录组学和代谢组学——结合体外实验，以研究KRT10在非小细胞肺癌（NSCLC）脑转移中的机制。我们观察到KRT10在NSCLC中的表达相对于正常组织升高。沉默KRT10显著降低了NSCLC细胞的迁移和侵袭。随后我们检查了肿瘤微环境，并识别出KRT10富集的转移微环境。NSCLC细胞通过KRT10与促转移的中性粒细胞胞外诱捕网（NET）DNA相互作用，随后确认了所涉及的特定DNA序列。此外还探究了KRT10在转移中的预测能力。总体而言，抑制KRT10可作为抑制NSCLC细胞脑转移的一种潜在治疗策略。
查看英文原文 English abstract
KRT10 is a keratin family protein that regulates epithelial structure and cellular differentiation. While the role of KRT10 in cancer metastasis has been previously reported, the specific mechanisms underlying its involvement remain unclear. In this study, we applied an integrated multi-omics strategy-including spatial transcriptomics and metabolomics-combined with in vitro assays to investigate the mechanism of KRT10 in non-small cell lung cancer (NSCLC) brain metastasis. We observed elevated KRT10 expression in NSCLC relative to normal tissues. Silencing KRT10 markedly reduced NSCLC cell migration and invasion. We then examined the tumor microenvironment and identified metastatic niches where KRT10 was concentrated. NSCLC cells interacted with pro-metastatic neutrophil extracellular trap (NET) DNA via KRT10, and the specific DNA sequences involved were subsequently confirmed. The predictive ability of KRT10 in metastasis was also explored. Overall, inhibiting KRT10 could serve as a potential therapeutic strategy to inhibit NSCLC cell brain metastasis.
利益披露 Disclosure
B. Chen, None..
L. Zhang, None..
K. Kiang, None.