Cellular and Molecular Life Sciences

, Volume 71, Issue 7, pp 1305–1314

Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation

  • Konstantin Knoblich
  • Hong-Xing Wang
  • Chandan Sharma
  • Anne L. Fletcher
  • Shannon J. Turley
  • Martin E. Hemler
Research Article

DOI: 10.1007/s00018-013-1444-8

Cite this article as:
Knoblich, K., Wang, HX., Sharma, C. et al. Cell. Mol. Life Sci. (2014) 71: 1305. doi:10.1007/s00018-013-1444-8

Abstract

Ablation of tetraspanin protein TSPAN12 from human MDA-MB-231 cells significantly decreased primary tumor xenograft growth, while increasing tumor apoptosis. Furthermore, TSPAN12 removal markedly enhanced tumor-endothelial interactions and increased metastasis to mouse lungs. TSPAN12 removal from human MDA-MB-231 cells also caused diminished association between FZD4 (a key canonical Wnt pathway receptor) and its co-receptor LRP5. The result likely explains substantially enhanced proteosomal degradation of β-catenin, a key effecter of canonical Wnt signaling. Consistent with disrupted canonical Wnt signaling, TSPAN12 ablation altered expression of LRP5, Naked 1 and 2, DVL2, DVL3, Axin 1, and GSKβ3 proteins. TSPAN12 ablation also altered expression of several genes regulated by β-catenin (e.g. CCNA1, CCNE2, WISP1, ID4, SFN, ME1) that may help to explain altered tumor growth and metastasis. In conclusion, these results provide the first evidence for TSPAN12 playing a role in supporting primary tumor growth and suppressing metastasis. TSPAN12 appears to function by stabilizing FZD4–LRP5 association, in support of canonical Wnt-pathway signaling, leading to enhanced β-catenin expression and function.

Keywords

TSPAN12Tetraspaninβ-cateninTumor growthTumor metastasis

Supplementary material

18_2013_1444_MOESM1_ESM.pdf (132 kb)
Supplementary material (PDF 132 kb)
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Supplementary material (PDF 27 kb)
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Supplementary material (DOCX 13 kb)
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Supplementary material (XLSX 37 kb)
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Supplementary material (XLSX 10 kb)

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Konstantin Knoblich
    • 1
  • Hong-Xing Wang
    • 1
  • Chandan Sharma
    • 1
  • Anne L. Fletcher
    • 1
    • 2
  • Shannon J. Turley
    • 1
  • Martin E. Hemler
    • 1
  1. 1.Cancer Immunology and AIDSDana-Farber Cancer InstituteBostonUSA
  2. 2.Monash University, Immunology and Stem Cell LaboratoriesClaytonAustralia