Colorectal cancer (CRC) as a multifactorial disease and its causal correlations with multiple signaling pathways

Wan, Maolin; Wang, Yu; Zeng, Zhi; Deng, Bo; Zhu, Bisheng; Cao, Ting; Li, Yukun; Xiao, Jianru; Han, Qin; Wu, Qing

doi:10.1042/bsr20200265

Cited by 63 publications

(45 citation statements)

References 165 publications

(193 reference statements)

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“…However, in two mouse models, such as spontaneous CRC in APC Min/+ mice and azoxymethane–dextran sodium sulfate (AOM-DSS)-induced CAC, the phospho-RMLC level was markedly elevated in tumor tissue as compared to normal intestinal mucosa [ 66 , 67 ]. In addition, evidence of activation of the RhoA/ROCK signaling axis in CRC suggests that RMLC phosphorylation could be increased during colonic tumorigenesis [ 17 , 68 ]. RhoA/ROCK signaling is a multi-modal regulator of the actin cytoskeleton, with RMLC being a major downstream effector of this signaling cascade [ 35 , 36 ].…”

Section: Conventional Myosinsmentioning

confidence: 99%

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

Naydenov

Lechuga

Huang

et al. 2021

Cancers

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Colorectal cancer (CRC) remains the third most common cause of cancer and the second most common cause of cancer deaths worldwide. Clinicians are largely faced with advanced and metastatic disease for which few interventions are available. One poorly understood aspect of CRC involves altered organization of the actin cytoskeleton, especially at the metastatic stage of the disease. Myosin motors are crucial regulators of actin cytoskeletal architecture and remodeling. They act as mechanosensors of the tumor environments and control key cellular processes linked to oncogenesis, including cell division, extracellular matrix adhesion and tissue invasion. Different myosins play either oncogenic or tumor suppressor roles in breast, lung and prostate cancer; however, little is known about their functions in CRC. This review focuses on the functional roles of myosins in colon cancer development. We discuss the most studied class of myosins, class II (conventional) myosins, as well as several classes (I, V, VI, X and XVIII) of unconventional myosins that have been linked to CRC development. Altered expression and mutations of these motors in clinical tumor samples and their roles in CRC growth and metastasis are described. We also evaluate the potential of using small molecular modulators of myosin activity to develop novel anticancer therapies.

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Section: Conventional Myosinsmentioning

confidence: 99%

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

Naydenov

Lechuga

Huang

et al. 2021

Cancers

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“…Growing evidence revealed that the ErbB and PI3K–Akt signaling pathways play vital roles in colorectal cancer by regulating microRNA, lncRNA, mRNA, etc. ( Szmida et al, 2015 ; Song et al, 2018 ; Wei et al, 2019 ; Zhong et al, 2019 ; Wan et al, 2020 ). These findings indicate that GI cancer is closely related to the ErbB and PI3K–Akt signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

m5C RNA Methylation Primarily Affects the ErbB and PI3K–Akt Signaling Pathways in Gastrointestinal Cancer

Xiang

Shen

et al. 2020

Front. Mol. Biosci.

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5-Methylcytosine (m5C) is a kind of methylation modification that occurs in both DNA and RNA and is present in the highly abundant tRNA and rRNA. It has an important impact on various human diseases including cancer. The function of m5C is modulated by regulatory proteins, including methyltransferases (writers) and special binding proteins (readers). This study aims at comprehensive study of the m5C RNA methylation-related genes and the main pathways under m5C RNA methylation in gastrointestinal (GI) cancer. Our result showed that the expression of m5C writers and reader was mostly up-regulated in GI cancer. The NSUN2 gene has the highest proportion of mutations found in GI cancer. Importantly, in liver cancer, higher expression of almost all m5C regulators was significantly associated with lower patient survival rate. In addition, the expression level of m5C-related genes is significantly different at various pathological stages. Finally, we have found through bioinformatics analysis that m5C regulatory proteins are closely related to the ErbB/PI3K–Akt signaling pathway and GSK3B was an important target for m5C regulators. Besides, the compound termed streptozotocin may be a key candidate drug targeting on GSK3B for molecular targeted therapy in GI cancer.

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“…The gut microenvironment homeostasis requires an intricate balance between cell proliferation, differentiation, and apoptosis processes in which several regulatory pathways are involved such as the Wnt, Notch, BMP, and Hedgehog signaling pathways [ 88 , 89 ]. Deregulation of these main signaling pathways can potentially determine a disruption of intestinal homeostasis and contribute to CRC development.…”

Section: Microbiotamentioning

confidence: 99%

What Is Known about Theragnostic Strategies in Colorectal Cancer

et al. 2021

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Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.

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Colorectal cancer (CRC) as a multifactorial disease and its causal correlations with multiple signaling pathways

Cited by 63 publications

References 165 publications

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

m5C RNA Methylation Primarily Affects the ErbB and PI3K–Akt Signaling Pathways in Gastrointestinal Cancer

What Is Known about Theragnostic Strategies in Colorectal Cancer

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