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解析大脑中富含 Ras 的同系物(Rheb1 和 Rheb2)的作用:通过雷帕霉素靶蛋白信号传导连接神经元动力学和癌症发病机制。

Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.

机构信息

College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea.

Department of BioHealthcare, Hwasung Medi-Science University, Hwaseong-si 18274, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Jan 25;25(3):1489. doi: 10.3390/ijms25031489.


DOI:10.3390/ijms25031489
PMID:38338768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10855792/
Abstract

Ras homolog enriched in brain (Rheb1 and Rheb2), small GTPases, play a crucial role in regulating neuronal activity and have gained attention for their implications in cancer development, particularly in breast cancer. This study delves into the intricate connection between the multifaceted functions of Rheb1 in neurons and cancer, with a specific focus on the mTOR pathway. It aims to elucidate Rheb1's involvement in pivotal cellular processes such as proliferation, apoptosis resistance, migration, invasion, metastasis, and inflammatory responses while acknowledging that Rheb2 has not been extensively studied. Despite the recognized associations, a comprehensive understanding of the intricate interplay between Rheb1 and Rheb2 and their roles in both nerve and cancer remains elusive. This review consolidates current knowledge regarding the impact of Rheb1 on cancer hallmarks and explores the potential of Rheb1 as a therapeutic target in cancer treatment. It emphasizes the necessity for a deeper comprehension of the molecular mechanisms underlying Rheb1-mediated oncogenic processes, underscoring the existing gaps in our understanding. Additionally, the review highlights the exploration of Rheb1 inhibitors as a promising avenue for cancer therapy. By shedding light on the complicated roles between Rheb1/Rheb2 and cancer, this study provides valuable insights to the scientific community. These insights are instrumental in guiding the identification of novel targets and advancing the development of effective therapeutic strategies for treating cancer.

摘要

脑富集 Ras 同源物(Rheb1 和 Rheb2),小分子 GTPases,在调节神经元活性方面发挥着关键作用,并且因其在癌症发展中的作用而受到关注,特别是在乳腺癌中。本研究深入探讨了 Rheb1 在神经元和癌症中的多方面功能之间的复杂联系,特别关注 mTOR 途径。它旨在阐明 Rheb1 在增殖、抗凋亡、迁移、侵袭、转移和炎症反应等关键细胞过程中的作用,同时承认 Rheb2 尚未得到广泛研究。尽管已经认识到了这些关联,但 Rheb1 和 Rheb2 之间复杂的相互作用及其在神经和癌症中的作用仍难以捉摸。本综述整合了目前关于 Rheb1 对癌症特征的影响的知识,并探讨了 Rheb1 作为癌症治疗中治疗靶点的潜力。它强调了深入理解 Rheb1 介导的致癌过程的分子机制的必要性,突出了我们理解中的现有差距。此外,该综述强调了探索 Rheb1 抑制剂作为癌症治疗的有前途的途径。通过阐明 Rheb1/Rheb2 与癌症之间的复杂关系,本研究为科学界提供了有价值的见解。这些见解有助于指导识别新的靶点,并推进治疗癌症的有效治疗策略的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/19e3591e0f03/ijms-25-01489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/084fe9d29b7a/ijms-25-01489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/9369bcef1b8d/ijms-25-01489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/1782d5a040a8/ijms-25-01489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/0f2bf055e2e3/ijms-25-01489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/19e3591e0f03/ijms-25-01489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/084fe9d29b7a/ijms-25-01489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/9369bcef1b8d/ijms-25-01489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/1782d5a040a8/ijms-25-01489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/0f2bf055e2e3/ijms-25-01489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594f/10855792/19e3591e0f03/ijms-25-01489-g005.jpg

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[10]
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本文引用的文献

[1]
NADPH Oxidase 2-Derived Reactive Oxygen Species Promote CD8+ T Cell Effector Function.

J Immunol. 2024-1-15

[2]
Statins markedly potentiate aminopeptidase inhibitor activity against (drug-resistant) human acute myeloid leukemia cells.

Cancer Drug Resist. 2023-7-4

[3]
Senescence program and its reprogramming in pancreatic premalignancy.

Cell Death Dis. 2023-8-17

[4]
Mutant KRAS Drives Immune Evasion by Sensitizing Cytotoxic T-Cells to Activation-Induced Cell Death in Colorectal Cancer.

Adv Sci (Weinh). 2023-2

[5]
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Genome. 2023-1-1

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Crucial Role of Oncogenic Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications.

Cells. 2022-7-13

[7]
Targeting farnesylation as a novel therapeutic approach in HRAS-mutant rhabdomyosarcoma.

Oncogene. 2022-5

[8]
KRAS as a Modulator of the Inflammatory Tumor Microenvironment: Therapeutic Implications.

Cells. 2022-1-24

[9]
RAS specific protease induces irreversible growth arrest via p27 in several KRAS mutant colorectal cancer cell lines.

Sci Rep. 2021-9-9

[10]
Lipid Metabolism Regulates Oxidative Stress and Ferroptosis in RAS-Driven Cancers: A Perspective on Cancer Progression and Therapy.

Front Mol Biosci. 2021-8-16

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