Proteomic characterization of annexin l (ANX1) and heat shock protein 27 (HSP27) as biomarkers for invasive hepatocellular carcinoma cells

Ruo Chiau Wang, Chien Yu Huang, Tai Long Pan, Wei Yu Chen, Chun Te Ho, Tsan Zon Liu, Yu Jia Chang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

To search for reliable biomarkers and drug targets for management of hepatocellular carcinoma (HCC), we performed a global proteomic analysis of a pair of HCC cell lines with distinct differentiation statuses using 2-DE coupled with MALDI-TOF MS. In total, 106 and 55 proteins were successfully identified from the total cell lysate and the cytosolic, nuclear and membrane fractions in well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) HCC clonal variants, respectively. Among these proteins, nine spots corresponding to proteins differentially expressed between HCC cell types were selected and confirmed by immunofluorescence staining and western blotting. Notably, Annexin 1 (ANX1), ANX-2, vimentin and stress-associated proteins, such as GRP78, HSP75, HSC-70, protein disulfide isomerase (PDI), and heat shock protein-27 (HSP27), were exclusively up-regulated in SK-Hep-1 cells. Elevated levels of ANX-4 and antioxidant/metabolic enzymes, such as MnSOD, peroxiredoxin, NADP-dependent isocitrate dehydrogenase, α-enolase and UDP-glucose dehydrogenase, were observed in HepG2 cells. We functionally demonstrated that ANX1 and HSP27 were abundantly overexpressed only in highly invasive types of HCC cells, such as Mahlavu and SK-Hep-1. Knockdown of ANX1 or HSP27 in HCC cells resulted in a severe reduction in cell migration. The in-vitro observations of ANX1 and HSP27 expressions in HCC sample was demonstrated by immunohistochemical stains performed on HCC tissue microarrays. Poorly differentiated HCC tended to have stronger ANX1 and HSP27 expressions than well-differentiated or moderately differentiated HCC. Collectively, our findings suggest that ANX1 and HSP27 are two novel biomarkers for predicting invasive HCC phenotypes and could serve as potential treatment targets.

Original languageEnglish
Article numbere0139232
JournalPLoS One
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 2 2015

Fingerprint

HSP27 Heat-Shock Proteins
Annexins
Biomarkers
hepatoma
heat shock proteins
Proteomics
proteomics
Hepatocellular Carcinoma
biomarkers
Cells
cells
Uridine Diphosphate Glucose Dehydrogenase
Proteins
Protein Disulfide-Isomerases
Peroxiredoxins
Isocitrate Dehydrogenase
Phosphopyruvate Hydratase
Vimentin
Microarrays
NADP

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Proteomic characterization of annexin l (ANX1) and heat shock protein 27 (HSP27) as biomarkers for invasive hepatocellular carcinoma cells. / Wang, Ruo Chiau; Huang, Chien Yu; Pan, Tai Long; Chen, Wei Yu; Ho, Chun Te; Liu, Tsan Zon; Chang, Yu Jia.

In: PLoS One, Vol. 10, No. 10, e0139232, 02.10.2015.

Research output: Contribution to journalArticle

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