Abstract

Golgi Protein 73 (GP73) is a serum biomarker for hepatocellular carcinoma (HCC), however its role in HCC is not clear. We report that GP73 promotes cell invasion, the hallmark of malignancy, through the upregulation of matrix metalloproteinase-13 (MMP-13). GP73 enhances MMP-13 expression through cAMP responsive element binding protein (CREB)-mediated transcription activation. Levels of GP73 and MMP-13 are increased and positively correlated in human HCC tissues. Augmented MMP-13 potentiates HCC cell metastasis. Thus, the GP73-CREB-MMP-13 axis potentiates cancer cell invasion and may be a target for HCC treatment.

Highlights

  • Hepatocellular carcinoma (HCC) is the fifth-most common cancer worldwide and the third-leading cause of cancer death [1]

  • These included 7 matrix metalloproteinases (MMPs) that we identified by qRT-PCR analysis and Western blot in HepG2 cells with ectopic Golgi protein 73 (GP73) expression and in HCCLM3 cells depleted of GP73

  • We found that 4 MMPs, MMP-1, MMP-2, matrix metalloproteinase-13 (MMP-13) and MMP-14, were increased after ectopic GP73 expression (Figure 1C) and decreased after depletion of GP73 expression

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth-most common cancer worldwide and the third-leading cause of cancer death [1]. Even though alpha-fetoprotein (AFP) is a specific serum marker for HCC, it is of minimal use as a diagnostic tool because its sensitivity is only around 50% [2]. Golgi protein 73 (GP73), named Golgi membrane protein 1 (Golm1) or Golgi phos­phoprotein 2 (GOLPH2), is proving to be a better biomarker for HCC [3,4,5]. Block and colleagues reported that serum GP73 (sGP73) levels were up-regulated in patients with hepatitis B virusrelated HCC [12]. Others, demonstrate that the sensitivity and specificity of sGP73 for the identification of HCC are superior to those of alpha-fetoprotein (AFP), especially in early HCC [4, 13]. We propose sGP73 as a novel marker for HCC diagnosis

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