Nat Commun: WSX1: A new tumor suppressor for hepatocellular carcinoma

Hepatocellular carcinoma (HCC), as one of the most common malignant tumors in the world, ranks fifth in cancer-related mortality
.

The occurrence and development of HCC is a multi-factor process, in which the genetic and epigenetic changes of regulatory genes will lead to the activation of oncogenes and the inactivation of tumor suppressor genes

Hepatocellular carcinoma (HCC), as one of the most common malignant tumors in the world, ranks fifth in cancer-related mortality

Unlike most other malignant tumors, HCC is a disease related to inflammation and immunity , which almost always occurs in the environment of inflamed liver fibrosis or cirrhosis
.

It is worth noting that the tightly controlled immune network that detects and eliminates transformed cells is often dysregulated in HCC

Immune Notably, the detection and elimination of transformed cells is tightly controlled in HCC immune network often offset is noteworthy that the detection and elimination of transformed cells of the immune disorder is often strictly controlled network in HCC

PD-L1 (programmed death ligand-1) is a key immune checkpoint protein that can bind to PD-1 (programmed death 1 receptor) on T cells and activate co-inhibitory signals, ultimately inhibiting the effect The function of T cells
.

Nevertheless, the relative mechanisms of the steady-state regulation of PD-L1 expression and its dysregulation in cancer are still poorly understood, and understanding the relevant regulatory mechanisms of PD-L1 will help to develop more effective treatment strategies

WSX1 is the receptor subunit of IL-27, which is widely expressed in immune cells and is closely related to immune response, but its function in non-immune cells is still unclear
.

WSX1 is the receptor subunit of IL-27, which is widely expressed in immune cells and is closely related to immune response, but its function in non-immune cells is still unclear
.

WSX1 is the receptor subunit of IL-27, which is widely expressed in immune cells and is closely related to immune response, but its function in non-immune cells is still unclear

WSX1 is down-regulated in HCC and is associated with poor patient prognosis

WSX1 is down-regulated in HCC and is associated with poor patient prognosis

In this study, the researchers found that WSX1 is highly expressed in human liver cells, but its expression level is down-regulated in HCC cells
.

In the NRAS/AKT-derived primary HCC mouse model, the researchers revealed the tumor suppressor effect of WSX1 independent of IL-27 , which mainly relies on the immune surveillance of CD8+ T cells, that is, by reducing tumor PD -Expression of L1 and related CD8+ T cell depletion

The tumor suppressor effect of WSX1 independent of IL-27 The tumor suppressor effect of WSX1 independent of IL-27

Mechanism studies have shown that WSX1 down-regulates the expression level of PI3K isoform PI3Kδ through transcription, inactivates AKT and reduces AKT-induced GSK3β inhibition
.

The activated GSK3β will further promote the degradation of PD-L1 and eventually cause the reduction of PD-L1

Related diagrams

Related diagrams

All in all, the results of the study revealed that WSX1 is a tumor suppressor, which can enhance the immune surveillance of the liver by blocking the PI3Kδ/AKT/GSK3β/PD-L1 pathway
.

The results of this study will also provide insights into the homeostasis regulation of the host immune response and contribute to the development of related cancer immunotherapies

WSX1 is a tumor suppressor, which can enhance the immune surveillance of the liver by blocking the PI3Kδ/AKT/GSK3β/PD-L1 pathway
.
WSX1 is a tumor suppressor, which can enhance the immune surveillance of the liver by blocking the PI3Kδ/AKT/GSK3β/PD-L1 pathway
.

Original source:

Wu, M.
, Xia, X.
, Hu, J.
et al.
WSX1 act as a tumor suppressor in hepatocellular carcinoma by downregulating neoplastic PD-L1 expression.
Nat Commun 12, 3500 (09 June 2021).

WSX1 act as a tumor suppressor in hepatocellular carcinoma by downregulating neoplastic PD-L1 expression.

 

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