Anastasia O Syrocheva, Konstantin I Ivanov, Victor S Laktyushkin, Neonila V Gorokhovets, Alessandro Parodi, Andrey A Zamyatnin
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引用次数: 0
摘要
组织蛋白酶B (CTSB)是一种溶酶体蛋白酶,也在溶酶体的酸性环境外起作用。在健康细胞中,CTSB在凋亡、自噬和维持细胞稳态等过程中起着至关重要的作用。然而,在癌症中,它通过促进侵袭和转移而显著促进疾病进展。本研究对CTSB及其天然抑制剂Stefin a (STFA)与肾癌细胞之间的关系进行了新的探索。我们首次通过研究STFA在非癌性胚胎肾细胞(Hek293T)、肾癌细胞(769p)和非肾癌细胞(Du145)中的表达,证实了CTSB对STFA表达的精确调控作用。这项研究强调了CTSB及其抑制剂之间复杂的相互作用,为肾癌生物学中发生的CTSB/STFA平衡提供了新的见解。在本研究中,我们通过CTSB功能获得、功能丧失和生化抑制的方法,同时检测了CTSB和STFA在各种癌细胞系中的mRNA和蛋白表达,以了解CTSB表达和活性在影响STFA水平及其相互亚细胞定位中的作用。我们发现癌细胞表现出对CTSB和STFA基因表达的调节受损。特别是,我们的研究结果表明,外源表达CTSB显著改变STFA水平,提示CTSB酶活性影响的反馈机制。重要的是,CTSB和STFA之间的关系在蛋白水平上得以保留,这表明在翻译水平上存在复杂的调控机制,缓解了转录失衡。本研究提供了癌细胞中CTSB和STFA之间相互作用的见解,并将其与胚胎细胞中的行为进行了比较,突出了CTSB异常表达如何影响其抑制剂,并推进了我们对肿瘤进展中这种平衡的理解。
Expression Interplay Between Cathepsin B and Its Natural Inhibitor Stefin A in Cancer and Embryonic Cell Lines.
Cathepsin B (CTSB) is a lysosomal protease that also operates outside the acidic environment of lysosomes. In healthy cells, CTSB plays a crucial role in processes such as apoptosis, autophagy, and the maintenance of cellular homeostasis. However, in cancer, it contributes significantly to disease progression by promoting invasion and metastasis. This study introduces a novel exploration of the relationship between CTSB and its natural inhibitor, Stefin A (STFA), renal cancer cells. For the first time, we demonstrated the precise regulatory influence of CTSB on STFA expression by investigating their expression in noncancerous embryonic renal cells (Hek293T), renal cancer cells (769p), and nonrenal cancer cells (Du145). This study highlights the intricate interplay between CTSB and its inhibitor, offering new insights into the CTSB/STFA balance that occurs in kidney cancer biology. In this study, we simultaneously examined the mRNA and protein expression of CTSB and STFA in various cancer cell lines by employing CTSB gain-of-function, loss-of-function, and biochemical inhibition approaches to understand the contributions of CTSB expression and activity in influencing STFA levels and their reciprocal subcellular localization. We found that cancer cells exhibited impaired regulation of CTSB and STFA gene expression. In particular, our results indicate that exogenous expression of CTSB significantly alters STFA levels, suggesting a feedback mechanism influenced by CTSB's enzymatic activity. Importantly, the relationship between CTSB and STFA is preserved at the protein level, indicating complex regulatory mechanisms mitigating transcriptional misbalances at the translational level. This study provides insight into the interplay between CTSB and STFA in cancer cells and compares it to their behavior in embryonic cells, highlighting how aberrant CTSB expression can influence its inhibitor and advancing our understanding of this balance in tumor progression.
期刊介绍:
Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect.
These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.