MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

Targeting the PI3K/Akt/mTOR Pathway in Hepatocellular Carcinoma

“…The two pathways interact at various signaling points; for example, Akt and mTOR (see review [ 103 ]) can be activated by alike growth factors and their concurrent dysregulation is a feature of some HCCs [ 104 ]. For further information, we refer readers to recent reviews on the role of Ras/MEK/ERK pathway in HCC [ 105 , 106 ]. The major components of the PI3K/Akt/MTOR pathway as discussed in the text are presented in Figure 1 .…”

Inhibition of RFX6 Suppresses the Invasive Ability of Tumor Cells Through the Notch Pathway and Affects Tumor Immunity in Hepatocellular Carcinoma

“…The pathogenesis study of HCC involves the genome, transcriptome, proteome and metabolism. A variety of key signaling pathways contribute to HCC tumorigenesis including the MEK/ERK (2), mitogen-activated protein kinases (MAPK) (3), mammalian target of rapamycin (mTOR) (4), JAK/STAT (5), Hedgehog (6), and TGF-b signaling pathways (7). Studies have sought to target key components in molecular and cellular pathways that are known to have aberrant signaling in HCC.…”

A Pleiotropic Role of the Hepatitis B Virus Core Protein in Hepatocarcinogenesis

“…Abnormal activation of these two pathways is heavily involved in hepatocarcinogenesis [70]. Thus, dysregulation of these pathways leads to inappropriate cellular behavior and participate in cellular transformation and carcinogenesis [69,71]. The frequency of mutations in the components of the MAPK/ERK signaling pathway is low, but frequent activation of the signaling has been found in HCC patients [71].…”