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Tumor Biology

, Volume 37, Issue 2, pp 2313–2320 | Cite as

Regulation of β-catenin transcription activity by leupaxin in hepatocellular carcinoma

  • Jia Shi
  • Wen-Jie Wu
  • Gang Hu
  • Xin Yu
  • Ge-Shu Yu
  • Han Lu
  • Ming-Liang Yang
  • Bin Liu
  • Zhi-Xiang Wu
Original Article

Abstract

In human cancers, β-catenin is accumulated in the nucleus and activates mRNA transcription of many oncogenic genes, such as cyclin D1 and c-myc. However, the mechanism of β-catenin-mediated transcriptional activation remains largely unknown. In the present study, we identified leupaxin, an adaptor protein sharing homology with the focal adhesion protein, as a novel coactivator for β-catenin in human hepatocellular carcinoma (HCC). We show that leupaxin could interact with β-catenin and enhance its transcriptional activity through recruitment of coactivator complex, including steroid receptor coactivator 1 (SRC-1) and P300. As a result, leupaxin regulates HCC cell proliferation and cell-cycle progression in the presence of intact Wnt/β-catenin signaling. Furthermore, leupaxin is overexpressed in HCC tissues and correlated with mRNA levels of cyclin D1 and c-myc. Therefore, this is the first demonstration of a role for the leupaxin in the regulation of HCC progression, at least in part, by enhancing β-catenin transcription activity.

Keywords

Hepatocellular carcinoma (HCC) Leupaxin β-catenin Coactivator Transcription activity 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation, People’s Republic of China, grant no. 31401185 (to Dr. Bin Liu) and no. 81402478 (to Dr. Zhi-Xiang Wu).

Conflicts of interest

None

Supplementary material

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Supplementary Figure 1

Overexpression of Leupaxin promotes cell proliferation in Hep3B cells. (A) Representative protein levels of Leupaxin in Hep3B cells transfected with adenoviruses containing Leupaxin (100 MOI) or empty vector (EV) for 36 hr. (B-C) Cell viability assays (B) and proliferation assays (C) in Hep3B cells transfected with adenoviruses containing Leupaxin (100 MOI) or empty vector (EV). (D) Relative mRNA levels of Cyclin D1 and c-myc in Hep3B cells overexpressing Leupaxin or empty vector (EV). (GIF 1 kb)

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High Resolution Image (TIFF 428 kb)
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Supplementary Figure 2

Knockdown of β-catenin blocked the roles of Leupaxin. (A) Representative protein levels of β-catenin in HuH7 cells transfected with small interfering RNA targeting β-catenin or negative control (NC) for 36 hr. (B-C) Cell viability assays (B) and proliferation assays (C) in HuH7 cells. Cells were transfected with small interfering RNA targeting β-catenin or negative control (NC) for 24 hr, and then transfected with Leupaxin or empty vector (EV) for another 24 hr. (D-E) Relative mRNA levels of Cyclin D1 (D) and c-myc (E) in HuH7 cells. (GIF 1 kb)

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High Resolution Image (TIFF 512 kb)
13277_2015_4060_Fig9_ESM.gif (2 kb)
Supplementary Figure 3

Knockdown of Leupaxin inhibits cell proliferation. (A) Representative protein levels of Leupaxin in Hep3B cells transfected with small interfering RNA targeting Leupaxin or negative control (NC) for 36 hr. (B-C) Cell viability assays (B) and proliferation assays (C) in Hep3B cells transfected with small interfering RNA targeting Leupaxin or negative control (NC). (D) Relative mRNA levels of Cyclin D1 and c-myc in Hep3B cells. (GIF 1 kb)

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High Resolution Image (TIFF 467 kb)
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Supplementary Figure 4

Subcellular distribution of β-catenin. HuH7 were transfected with adenoviruses containing Leupaxin (100 MOI) or empty vector (EV) for 36 hr. α-Tubulin and Histone H3 were used as loading controls for cytoplasmic and nuclear lysates, respectively. (GIF 7 kb)

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High Resolution Image (TIFF 940 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jia Shi
    • 1
  • Wen-Jie Wu
    • 1
  • Gang Hu
    • 2
  • Xin Yu
    • 2
  • Ge-Shu Yu
    • 2
  • Han Lu
    • 3
  • Ming-Liang Yang
    • 4
  • Bin Liu
    • 2
  • Zhi-Xiang Wu
    • 1
  1. 1.Department of Pediatric SurgeryXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of MedicineHubei Polytechnic UniversityHuangshiPeople’s Republic of China
  3. 3.Department of Anesthesiology, Ruijin HospitalShanghai Jiao Tong University School of Medicine (SJTU-SM)ShanghaiPeople’s Republic of China
  4. 4.Department of AnesthesiologyJianli Second People’s HospitalJianliPeople’s Republic of China

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