KLK7通过MAPK/ERK通路参与EMT对甲状腺乳头状癌细胞的迁移和侵袭。

IF 3.2 3区 医学 Q2 ONCOLOGY Journal of Cancer Pub Date : 2025-02-11 eCollection Date: 2025-01-01 DOI:10.7150/jca.101555
Min Li, Zi-Wen Li, Jia-Yin Song, Yu Bin, Tao Ni, Gang Xue, Xu Lin, Jing-Fang Wu
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引用次数: 0

摘要

目的:KLK7,也被称为Kallikrein 7,是一种被归类为丝氨酸蛋白酶的分泌酶。早期的研究表明,KLK7、KLK10和KLK11与甲状腺乳头状癌(PTC)患者的生存率和免疫反应有关。本研究检测了KLK7,探讨了其作用和表达,并评估了其作为PTC治疗靶点的可行性。方法:首先,我们利用生物信息学技术检测了KLK7在PTC中的表达及其可能的功能。研究人员检测了KLK7对PTC癌症特征的影响,并利用免疫组织化学和生长曲线分析等方法探讨了KLK7是否通过PTC的MAPK/ERK途径影响上皮-间质转化(EMT)过程。最后,我们利用裸鼠建立了一个模型来证实KLK7对PTC的影响。结果:我们的研究表明,KLK7在THCA组织中存在变异,KLK7相关基因具有参与PTC蛋白合成、遗传变异、mRNA降解和免疫微环境的作用。KLK7在PTC组织中表达上调,与临床分期和淋巴结转移呈正相关。此外,KLK7的抑制显著降低了PTC细胞的增殖、迁移和侵袭性。值得注意的是,沉默KLK7降低了ERK1/2的磷酸化和EMT的抑制。体内实验进一步支持了这些发现。KLK7可能作为PTC患者有效的治疗靶点和预测性生物标志物。结论:KLK7可能通过MAPK/ERK信号通路影响EMT,从而影响PTC细胞的生长、迁移和侵袭性,从而在PTC癌变进程中发挥重要作用。KLK7似乎是PTC治疗中一个很有前途的靶点。
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KLK7 Involvement in Thyroid Papillary Carcinoma Cell Migration and Invasion by EMT via MAPK/ERK Pathways.

Purpose: KLK7, also known as Kallikrein 7, is a secreted enzyme classified as a serine protease. Earlier studies have indicated that KLK7, KLK10, and KLK11 are linked to the survival rates and immune reactions of individuals with papillary thyroid cancer (PTC). This research examines KLK7, investigating its role and expression, and evaluates its viability as a treatment target for PTC. Methods: Initially, we examined the expression and possible functions of KLK7 in PTC using bioinformatics techniques. Researchers examined the impact of KLK7 on the cancer characteristics of PTC and explored if KLK7 influences the Epithelial-mesenchymal transition (EMT) process via the MAPK/ERK pathway in PTC using methods like immunohistochemistry and growth curve analysis. Ultimately, a model using a nude mouse was conducted to confirm the impact of KLK7 on PTC. Results: Our research demonstrated that KLK7 exhibited variations in THCA tissues, and KLK7-related genes had the role of participating in protein synthesis, genetic variation, mRNA degradation and immune microenvironment of PTC. KLK7 was upregulated in PTC tissues and positively associated with clinical stage and lymph node metastasis. Furthermore, the inhibition of KLK7 significantly diminished the proliferation, migration, and invasiveness of PTC cells. Notably, silencing KLK7 reduced phosphorylation of ERK1/2 and suppression of EMT. In vivo experiments further supported these findings. KLK7 might serve as an efficacious therapeutic target and predictive biomarker for PTC patients. Conclusion: KLK7 could be essential in the cancerous advancement of PTC by influencing the EMT via the MAPK/ERK signaling pathway, thereby impacting the growth, migration, and invasiveness of PTC cells. KLK7 appears to be a promising candidate for targeting in PTC therapy.

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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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