Roles of protein tyrosine phosphatases in hepatocellular carcinoma progression (Review)

Abstract

Hepatocellular carcinoma (HCC) represents almost 80% of all liver cancers, is the sixth most common cancer and is the second‑highest cause of cancer‑related deaths worldwide. Protein tyrosine phosphatases (PTPs), which are encoded by the largest family of phosphatase genes, play critical roles in cellular responses and are implicated in various signaling pathways. Moreover, PTPs are dysregulated and involved in various cellular processes in numerous cancers, including HCC. Kinases and phosphatases are coordinators that modulate cell activities and regulate signaling responses. There are multiple interacting signaling networks, and coordination of these signaling networks in response to a stimulus determines the physiological outcome. Numerous issues, such as drug resistance and inflammatory reactions in the tumor microenvironment, are implicated in cancer progression, and the role of PTPs in these processes has not been well elucidated. Therefore, the present review focused on discussing the relationship of PTPs with inflammatory cytokines and chemotherapy/targeted drug resistance, providing detailed information on how PTPs can modulate inflammatory reactions and drug resistance to influence progression in HCC.

Keywords: drug resistance; hepatocellular carcinoma; inflammation; protein tyrosine phosphatases.

Figure 1.

PTPs modulate cytokine secretions via various signaling pathways. (A) PTPN6 and (B) PTPRO can induce IL-6 secretion via upregulated STAT3 phosphorylation and downregulated JAK2/STAT3 pathways, respectively. (C) PTP1B can activate NF-κB signaling to induce IL-1β/IL-6 and TNF-α secretions. PTPs, protein tyrosine phosphatases; PTPN6, protein tyrosine phosphatase, non-receptor type 6; PTPRO, protein tyrosine phosphatase receptor type O.

Figure 2.

PTPs regulate drug resistance through numerous signaling pathways. (A) PTPN6 induces cell apoptosis and HCC progression through JAK/STAT3 signaling. (B) PTPN11 influences cell senescence and tumor cell growth via the STAT3/MEK/ERK/NF-κB and PI3K/Akt/mTOR pathways. (C) PTPRO regulates HCC development and cell autophagy via the STAT3 and PI3K pathways. PTP, PTPs, protein tyrosine phosphatases; PTPN6, protein tyrosine phosphatase, non-receptor type 6; PTPN11, protein tyrosine phosphatase, non-receptor type 11; PTPRO, protein tyrosine phosphatase receptor type O; HCC, hepatocellular carcinoma.