鸟嘌呤核苷酸交换因子与结肠肿瘤。

IF 4.6 2区 生物学 Q2 CELL BIOLOGY
Frontiers in Cell and Developmental Biology Pub Date : 2024-10-18 eCollection Date: 2024-01-01 DOI:10.3389/fcell.2024.1489321
Lea-Pearl Njei, Natalia Sampaio Moura, Alyssa Schledwitz, Kelly Griffiths, Kunrong Cheng, Jean-Pierre Raufman
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引用次数: 0

摘要

尽管在诊断和治疗方面取得了许多进步,但结直肠癌(CRC)仍然是美国男性和女性癌症死亡的第二大原因。令人担忧的是,由于目前尚不清楚的原因,这种疾病的发病人群已转向年轻人。因此,了解 CRC 发病和进展的分子机制并将这些发现用于治疗仍是当务之急。在此,我们对鸟嘌呤核苷酸交换因子(GEFs)的规范和非规范作用在 CRC 演变中发挥重要作用的证据进行了批判性回顾。Rho GEF GTPases 可在非活性 GDP 结合态和活性 GTP 结合态之间切换,在包括 CRC 在内的多种癌症中普遍存在过表达和激活现象,可能是可治疗的靶点。除了全面回顾这一领域,我们还重点研究了参与调节正常细胞和肿瘤细胞关键功能的 Rho/Rac GEFs,如细胞极性、囊泡贩运、细胞周期调控和转录动态。这类 Rho/Rac GEF 的主要例子包括 Cdc42/Rac1 的 Rho 家族 GEF βPak-interacting 交换因子(βPix)、Tiam1、GEF-H1、RGNEF 以及与 CRC 的发展和进程有关的其他 GEF。通过分析,我们探讨了这些发现如何填补了结肠癌发生的分子基础方面的知识空白,以及如何利用这些发现治疗晚期 CRC。最后,我们探讨了 GEFs 作为 CRC 生物标记物和治疗靶点的潜在未来研究方向。在这方面,利用 GEFs 的非规范作用似乎提供了一个相对尚未开发的机会,需要进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Guanine nucleotide exchange factors and colon neoplasia.

Despite many diagnostic and therapeutic advances, colorectal cancer (CRC) remains the second leading cause of cancer death for men and women in the United States. Alarmingly, for reasons currently unknown, the demographics of this disease have shifted towards a younger population. Hence, understanding the molecular mechanisms underlying CRC initiation and progression and leveraging these findings for therapeutic purposes remains a priority. Here, we review critically the evidence that canonical and noncanonical actions of guanine nucleotide exchange factors (GEFs) play important roles in CRC evolution. Rho GEF GTPases, which switch between inactive GDP-bound and active GTP-bound states, are commonly overexpressed and activated in a variety of cancers, including CRC, and may be tractable therapeutic targets. In addition to comprehensively reviewing this field, we focus on Rho/Rac GEFs that are involved in regulating key functions of normal and neoplastic cells like cell polarity, vesicle trafficking, cell cycle regulation, and transcriptional dynamics. Prime examples of such Rho/Rac GEFs include βPak-interacting exchange factor (βPix), a Rho family GEF for Cdc42/Rac1, Tiam1, GEF-H1, RGNEF, and other GEFs implicated in CRC development and progression. Throughout this analysis, we explore how these findings fill key gaps in knowledge regarding the molecular basis of colon carcinogenesis and how they may be leveraged to treat advanced CRC. Lastly, we address potential future directions for research into the role of GEFs as CRC biomarkers and therapeutic targets. In this regard, leveraging the noncanonical actions of GEFs appears to provide a relatively unexplored opportunity requiring further investigation.

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来源期刊
Frontiers in Cell and Developmental Biology
Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
9.70
自引率
3.60%
发文量
2531
审稿时长
12 weeks
期刊介绍: Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.
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