Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar.
College of Medicine, QU Health, Qatar University, Doha 2713, Qatar.
Int J Mol Sci. 2020 Dec 24;22(1):130. doi: 10.3390/ijms22010130.
Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.
结直肠癌（CRC）是第三大常见癌症，也是全球癌症相关死亡率的第二大主要原因。尽管现代研究能够阐明 CRC 的发病机制并提供增强的筛查策略，但 CRC 的患病率仍在上升。研究表明，CRC 中存在几种细胞信号通路失调，导致恶性表型的发生。因此，分析参与 CRC 转移的信号通路对于阐明 CRC 进展和药物治疗的潜在机制是必要的。本综述重点介绍了与 CRC 进展和转移相关的靶基因以及各种细胞信号通路，包括 Wnt/β-catenin、p53、TGF-β/SMAD、NF-κB、Notch、VEGF 和 JAKs/STAT3。此外，还回顾了与调节细胞周期、转录、细胞凋亡和血管生成以及侵袭和转移等各种细胞机制相关的信号通路中甲基化模式的改变。迄今为止，对基因组和表观基因组不稳定性的理解已经确定了候选生物标志物，这些标志物已在 CRC 管理的常规临床应用中得到验证。然而，更好地了解 CRC 的发生和进展可以帮助开发早期检测分子标志物和风险分层方法，以改善 CRC 患者的临床护理。
