Molecular crossroads: identifying MAPK proteins bridging SMAD and dopamine pathways in breast cancer.

IF 3.4 3区 生物学 Q3 CELL BIOLOGY
Cell Cycle Pub Date : 2025-07-01 Epub Date: 2025-08-28 DOI:10.1080/15384101.2025.2549097
Przemysław Borawski, Tomasz Sirek, Agata Sirek, Nikola Zmarzły, Robert Nowakowski, Piotr Ossowski, Michał Chalcarz, Kacper Boron, Dariusz Boron, Krzysztof Bereza, Konrad Dziobek, Nina Skalska-Dziobek, Piotr Wyrobiec, Beniamin Oskar Grabarek
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引用次数: 0

Abstract

The transforming growth factor-beta (TGF-β)/SMAD signaling pathway, mitogen-activated protein kinase (MAPK) signaling cascade, and dopamine receptor activity are all implicated in tumor progression. This study investigates molecular interactions among these pathways, identifying MAPK proteins that bridge SMAD and dopamine signaling in the context of breast cancer pathogenesis. A cohort of 405 breast cancer patients was categorized into molecular subtypes: luminal A (n = 130), luminal B HER2-negative (n = 100), luminal B HER2-positive (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (TNBC; n = 43). Transcriptomic profiling using microarrays and bioinformatics-based network analysis revealed differentially expressed genes across subtypes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate 11 key transcripts, and protein expression was quantified by enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) regulatory interactions were analyzed to assess post-transcriptional modulation. Among 167 differentially expressed genes, 14 were consistently altered across all subtypes. These included cell division cycle 42 (CDC42), KRAS proto-oncogene, GTPase (KRAS), and transforming growth factor beta 1 (TGFB1), which were upregulated, as well as fibroblast growth factor 2 (FGF2), fibroblast growth factor 7 (FGF7), and insulin-like growth factor 1 (IGF1), which were downregulated. miRNA analysis revealed miR-221, miR-222, and miR-16-5p as regulators of these pathways. ELISA confirmed reduced KIT, IGF1, and FGF family proteins in tumor tissues, with KRAS significantly upregulated. Protein interaction analysis highlighted key hubs linking MAPK, SMAD, and dopamine signaling. This study elucidates crucial molecular intersections between MAPK, SMAD, and dopamine pathways, identifying potential biomarkers and therapeutic targets for breast cancer.

分子十字路口:鉴定乳腺癌中连接SMAD和多巴胺通路的MAPK蛋白。
转化生长因子-β (TGF-β)/SMAD信号通路、丝裂原活化蛋白激酶(MAPK)信号级联以及多巴胺受体活性都与肿瘤进展有关。本研究研究了这些通路之间的分子相互作用,确定了在乳腺癌发病机制中连接SMAD和多巴胺信号的MAPK蛋白。405例乳腺癌患者被分为分子亚型:腔内A型(n = 130)、腔内B型her2阴性(n = 100)、腔内B型her2阳性(n = 96)、非腔内her2阳性(n = 36)和三阴性乳腺癌(TNBC, n = 43)。使用微阵列和基于生物信息学的网络分析的转录组学分析揭示了不同亚型的差异表达基因。采用定量反转录聚合酶链反应(qRT-PCR)对11个关键转录物进行验证,并采用酶联免疫吸附试验(ELISA)对蛋白表达进行定量分析。分析MicroRNA (miRNA)调控相互作用以评估转录后调节。在167个差异表达基因中,14个在所有亚型中一致改变。其中包括细胞分裂周期42 (CDC42)、KRAS原癌基因、GTPase (KRAS)和转化生长因子β 1 (TGFB1)的上调,以及成纤维细胞生长因子2 (FGF2)、成纤维细胞生长因子7 (FGF7)和胰岛素样生长因子1 (IGF1)的下调。miRNA分析显示miR-221、miR-222和miR-16-5p是这些通路的调节因子。ELISA证实肿瘤组织中KIT、IGF1和FGF家族蛋白减少,KRAS显著上调。蛋白质相互作用分析强调了连接MAPK、SMAD和多巴胺信号的关键枢纽。这项研究阐明了MAPK、SMAD和多巴胺通路之间的关键分子交叉点,确定了乳腺癌的潜在生物标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Cycle
Cell Cycle 生物-细胞生物学
CiteScore
7.70
自引率
2.30%
发文量
281
审稿时长
1 months
期刊介绍: Cell Cycle is a bi-weekly peer-reviewed journal of high priority research from all areas of cell biology. Cell Cycle covers all topics from yeast to man, from DNA to function, from development to aging, from stem cells to cell senescence, from metabolism to cell death, from cancer to neurobiology, from molecular biology to therapeutics. Our goal is fast publication of outstanding research.
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