Golgi Phosphoprotein 73: The Driver of Epithelial-Mesenchymal Transition in Cancer.

Yiming Liu,Shiyao Liu,Hongchuan Jin,Xinyang Hu,Zhi Chen,Sining Zhou

doi:10.3389/fonc.2021.783860

Abstract

Golgi phosphoprotein 73 (GP73, also termed as GOLM1 or GOLPH2) is a glycosylated protein residing on cis-Golgi cisternae and highly expressed in various types of cancer tissues. Since GP73 is a secretory protein and detectable in serum derived from cancer patients, it has been regarded as a novel serum biomarker for the diagnosis of different cancers, especially hepatocellular carcinoma (HCC). However, the functional roles of GP73 in cancer development are still poorly understood. In recent years, it has been discovered that GP73 acts as a multifunctional protein-facilitating cancer progression, and strikingly, it has been identified as a leading factor promoting epithelial-mesenchymal transition (EMT) of cancer cells and causing cancer metastasis. In this review, we have overviewed the latest findings of the functional roles of GP73 in elevating cancer progression, especially in facilitating EMT and cancer metastasis through modulating expression, transactivation, and trafficking of EMT-related proteins. In addition, unsolved research fields of GP73 have been lightened, which might be helpful to elucidate the regulatory mechanisms of GP73 on EMT and provide potential approaches in therapeutics against cancer metastasis.

Highlights

In the past decades, cancer has been ranked as the primary cause of death and the largest health problem worldwide [1]
RNA sequencing in this study has revealed that knockdown of Golgi phosphoprotein 73 (GP73) reduces the levels of matrix metalloproteinase-7 (MMP-7) and CD44, two factors involved in cell invasion, heterotypic adhesion, and hepatocellular carcinoma (HCC) metastasis; the regulatory mechanisms are unclear [94,95,96]
Following studies have focused on the mechanisms of how GP73 facilitates cancer metastasis, and they have discovered that highly expressed GP73 upregulates the levels of N-cadherin, vimentin, and matrix metalloproteinases (MMPs)-13 in HCC cells, which prove that GP73 surely serves as a multifunctional factor modulating the expression of epithelial-mesenchymal transition (EMT)-related proteins (Table 4)

Summary

Introduction

Cancer has been ranked as the primary cause of death and the largest health problem worldwide [1]. A recent study in our group has uncovered that hypoxia upregulates oncogenic protein c-Myc and transactivates GP73 in a mildly hypoxic tumor microenvironment, which suggests that GP73 might be activated to play critical roles against adverse circumstances and promote the survival of cancer cells (Figure 2) [19]. Following studies have focused on the mechanisms of how GP73 facilitates cancer metastasis, and they have discovered that highly expressed GP73 upregulates the levels of N-cadherin, vimentin, and MMP-13 in HCC cells, which prove that GP73 surely serves as a multifunctional factor modulating the expression of EMT-related proteins (Table 4).

Results

Conclusion