The functional landscape of Golgi membrane protein 1 (GOLM1) phosphoproteome reveal GOLM1 regulating P53 that promotes malignancy

Qi Song,Junlan Wang,Ying Xiong,Xiang He,Guoping Li,Lei Zhang,Elaine Lai-Han Leung

doi:10.1038/s41420-021-00422-2

Abstract

Golgi membrane protein 1 (GOLM1) was implicated in carcinogenesis of multiple types of cancer. However, Phosphoproteome landscapes of GOLM1 overexpression in lung cancer remain largely unknown. In this study, using data from the Cancer Genome Atlas (TCGA) and phosphoproteome, we systematically evaluated the feature of GOLM1 and studied its prognostic value in non-small cell lung cancer (NSCLC). The proliferation, migration, and invasion capacities in PC9 cell with GOLM1 overexpression were determined using Trans-well system assay. Tumor engrafts was visualized in mice models and confirmed by ex vivo. An increased expression of GOLM1 had shorter overall survival (OS) in patients with NSCLC in TCGA database. GOLM1 in single gene set enrichment analysis (GSEA) related to adherent’s junction, cell cycle, and pathway in cancer. Overexpression of GOLM1 in GOLM1OE PC9 cells promoted cell proliferation, migration, and invasion. Decreased migration and invasion potential were also observed in knockdown of GOLM1 in GOLM1KD PC9 cells in migration assay. An increased expression of GOLM1 could significantly increase the growth of tumor in xenograft mice models. phosphoproteome analysis showed 239 upregulated and 331 downregulated Phosphorylated proteins in GOLM1OE PC9 cells. Overexpression of GOLM1 in GSEA was significantly related to P53 in MAPK signaling pathway. Overexpression of GOLM1enhanced the phosphorylation of P53 protein at site S315 but inhibited the formation of P53 tetramers. These results indicate that overexpression GOLM1 enhances non-small-cell carcinoma aggressiveness through inhibited the formation of P53 tetramer.

Highlights

Across the globe, regardless of cancer morbidity or mortality, lung cancer always ranks first among malignant tumors
Through data mining in the Cancer Genome Atlas (TCGA), we found that Golgi membrane protein 1 (GOLM1) is associated with lung cancer, especially lung adenocarcinoma, and the expression level of GOLM1 is causally related to overall survival
We found that GOLM1 expression in both lung adenocarcinoma and lung squamous cell carcinoma was significantly higher than that in the normal control group, and the different level in lung adenocarcinoma was statistically significantly higher than that in lung squamous cell carcinoma (Fig. 1C)

Summary

Introduction

Regardless of cancer morbidity or mortality, lung cancer always ranks first among malignant tumors. Prediction based on reliable data, there will be 2.1 million new cases of lung cancer and 1.8 million deaths in 2018, which will be close to one-fifth (18.4%) of cancer deaths[1]. It is well established that there is no effective early diagnostic biomarker for lung cancer. To find new biomarkers that play an active role in early detection of cancer has become a major research hotspot. Encode protein of GOLM1 is a type II Golgi transmembrane protein which named Golgi phosphoprotein 2 or Golgi protein 738. The expression of this encoded protein has been observed to be upregulated in lung cancer tissues[9,10]. GOLM1 has the potential to become a new tumor biomarker

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Discussion

Conclusion