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

Mao-Lin Wan,Yu Wang,Yu-Kun Li,Bo Deng,Zhi Zeng,Bi-Sheng Zhu,Jiao Xiao,Qing Wu,Ting Cao,Qi Han

doi:10.1042/bsr20200265

Abstract

Colorectal cancer (CRC) is the third most common malignancy and one of the leading causes of cancer-related death among men worldwide. CRC is a multifactor digestive pathology, which is a huge problem faced not only by clinicians but also by researchers. Importantly, a unique feature of CRC is the dysregulation of molecular signaling pathways. To date, a series of reviews have indicated that different signaling pathways are disordered and have potential as therapeutic targets in CRC. Nevertheless, an overview of the function and interaction of multiple signaling pathways in CRC is needed. Therefore, we summarized the pathways, biological functions and important interactions involved in CRC. First, we investigated the involvement of signaling pathways, including Wnt, PI3K/Akt, Hedgehog, ErbB, RHOA, Notch, BMP, Hippo, AMPK, NF-κB, MAPK and JNK. Subsequently, we discussed the biological function of these pathways in pathophysiological aspects of CRC, such as proliferation, apoptosis and metastasis. Finally, we summarized important interactions among these pathways in CRC. We believe that the interaction of these pathways could provide new strategies for the treatment of CRC.

Highlights

Colorectal cancer (CRC) is the third most common malignancy worldwide and is one of the leading causes of cancer-related death [1]
Many investigators believe that the RHOA signaling pathway, in its carcinogenic role, has a complex interaction with many cancers via proliferation, apoptosis, metastasis, dedifferentiation and polarization [77,78,79], a recent study suggests that it has totally different function in CRC than it does in other cancers [80]
A large number of pathophysiological studies have confirmed that dysregulation of signaling pathways plays a significant role in CRC, promoting cell proliferation and migration but inhibiting cell differentiation and apoptosis through multiple interactions and feedback loops [159,160]

Summary

Introduction

Colorectal cancer (CRC) is the third most common malignancy worldwide and is one of the leading causes of cancer-related death [1]. Previous studies have indicated that CRC progression is mediated by the dysregulation of many signaling pathways, including Wnt [19], PI3K/Akt [20,21], Hedgehog [22], ErbB [23], RHOA [24], Notch [25], BMP [26], Hippo [27], AMPK [28], NF-κB [29], MAPK [3] and JNK [30]. The PI3K/Akt pathway can inhibit the Hippo pathway by promoting the phosphorylation of YAP to accelerate colon cancer cell proliferation [59].

Results

Conclusion