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IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-03-04 DOI:10.1186/s12964-025-02064-8

Katarzyna Horodecka, Liliana Czernek, Łukasz Pęczek, Magdalena Klink

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引用次数: 0

摘要

背景：信号通路的改变助长了黑色素瘤的生长和恶化。因此，了解这些过程对于制定有效的治疗策略至关重要。众所周知，RAB27A 和 RAB27B 具有致癌作用，可调节包括黑色素瘤在内的各种癌症的癌细胞增殖、侵袭和耐药性。这些蛋白被认为是囊泡运输的协调者，但它们在细胞信号传导中的功能却鲜为人知。因此，我们旨在研究 RAB27 与黑色素瘤细胞中的致癌蛋白或信号蛋白之间的关系：我们在 SkMel28、A375 和源自患者的 DMBC12 黑色素瘤细胞系中产生了 RAB27A 基因敲除（KO）。此外，我们还创建了RAB27A/B双基因敲除（dKO）的A375细胞系。首先，我们应用蛋白质组剖析器阵列来鉴定 RAB27A/B 缺失时差异表达的蛋白质。随后，我们利用 RT-PCR、Western 印迹和流式细胞术挑选出特定蛋白质进行进一步深入分析：结果：我们发现，在细胞系依赖水平上，沉默 RAB27 会显著降低与增殖、侵袭、血管生成、粘附或 EMT 相关的各种细胞内蛋白的水平。其中，我们观察到 RAB27 的表达与表皮生长因子受体、HER2 和 HER3 之间存在联系。HER受体水平的改变通过减少AKT和ERK1/2蛋白的磷酸化扰乱了下游信号通路：我们的研究结果提供了以前未发表过的新数据，说明了黑色素瘤细胞中 HER 家族受体表达与潜在活性之间的关系以及 RAB27 的参与。

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Revealing the role of RAB27 in HER receptor family expression and signaling in melanoma cells.

Background: Alterations in signalling pathways fuel the growth and progression of melanoma. Therefore, understanding these processes is essential for developing effective treatment strategies. RAB27A and RAB27B are known to possess oncogenic effects by modulating cancer cell proliferation, invasion and drug resistance in various types of cancer, including melanoma. These proteins are mostly acknowledged as coordinators of the vesicular trafficking, however, their function in cellular signaling is less recognized. Therefore we aimed to investigate the relationship between RAB27 and oncogenic or signalling proteins in melanoma cells.

Methods: We generated RAB27A knockout (KO) in SkMel28, A375, and patient-derived DMBC12 melanoma cell lines. Additionally, a double RAB27A/B knockout (dKO) A375 cell line was created. Firstly, we applied the Proteome Profiler array to identify proteins differentially expressed upon RAB27A/B loss. Subsequently, we picked selected specific proteins for a further in-depth analysis using RT-PCR, Western blot, and flow cytometry.

Results: We found that silencing RAB27 markedly decreased the levels of various intracellular proteins linked with proliferation, invasion, angiogenesis, adhesion, or EMT at a cell-line dependent level. Among others, we observed a link between the expression of RAB27 and EGFR, HER2 and HER3. Altered levels of HER receptors disturbed the downstream signaling pathways by reducing the phosphorylation of AKT and ERK1/2 proteins.

Conclusions: Our findings present novel, previously unpublished data on the relationship between HER family receptor expression and potential activity, and the involvement of RAB27 in melanoma cells.

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.