Tetraspanin CD151 plays a key role in skin squamous cell carcinoma

Q. Li, X. H. Yang, F. Xu, C. Sharma, H. X. Wang, K. Knoblich, I. Rabinovitz, S. R. Granter, M. E. Hemler

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Here we provide the first evidence that tetraspanin CD151 can support de novo carcinogenesis. During two-stage mouse skin chemical carcinogenesis, CD151 reduces tumor lag time and increases incidence, multiplicity, size and progression to malignant squamous cell carcinoma (SCC), while supporting both cell survival during tumor initiation and cell proliferation during the promotion phase. In human skin SCC, CD151 expression is selectively elevated compared with other skin cancer types. CD151 support of keratinocyte survival and proliferation may depend on activation of transcription factor STAT3 (signal transducers and activators of transcription), a regulator of cell proliferation and apoptosis. CD151 also supports protein kinase C (PKC)α- α6β4 integrin association and PKC-dependent β4 S1424 phosphorylation, while regulating α6β4 distribution. CD151-PKCα effects on integrin β4 phosphorylation and subcellular localization are consistent with epithelial disruption to a less polarized, more invasive state. CD151 ablation, while minimally affecting normal cell and normal mouse functions, markedly sensitized mouse skin and epidermoid cells to chemicals/drugs including 7,12-dimethylbenz anthracene (mutagen) and camptothecin (topoisomerase inhibitor), as well as to agents targeting epidermal growth factor receptor, PKC, Jak2/Tyk2 and STAT3. Hence, CD151 'co-targeting' may be therapeutically beneficial. These findings not only support CD151 as a potential tumor target, but also should apply to other cancers utilizing CD151/laminin-binding integrin complexes.

Original languageEnglish
Pages (from-to)1772-1783
Number of pages12
Issue number14
StatePublished - Apr 4 2013

Bibliographical note

Funding Information:
We thank Dr R Bronson for assistance with mouse histopathology, Dr Julie Aldridge for assistance with statistical analyses, and Drs David Frank, Sarah Walker and coworkers for nifuroxazide, ST3–01, assistance with STAT3 functional assay and helpful discussions. This work was supported by NIH grant CA42368 (to MEH), and a SG Komen Career Catalyst Award (to XHY).


  • PKCa
  • STAT3
  • chemical carcinogenesis
  • integrin a6b4
  • skin squamous cell carcinoma
  • tetraspanin CD151

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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