The interplay between p66Shc, reactive oxygen species and cancer cell metabolism

Eur J Clin Invest. 2015 Jan;45 Suppl 1:25-31. doi: 10.1111/eci.12364.


The adaptor protein p66Shc links membrane receptors to intracellular signalling pathways and has the potential to respond to energy status changes and regulate mitogenic signalling. Initially reported to mediate growth signals in normal and cancer cells, p66Shc has also been recognized as a pro-apoptotic protein involved in the cellular response to oxidative stress. Moreover, it is a key element in processes such as cancer cell proliferation, tumor progression, metastasis and metabolic reprogramming. Recent findings on the role of p66Shc in the above-mentioned processes have been obtained through the use of various tumor cell types, including prostate, breast, ovarian, lung, colon, skin and thyroid cancer cells. Interestingly, the impact of p66Shc on the proliferation rate was mainly observed in prostate tumors, while its impact on metastasis was mainly found in breast cancers. In this review, we summarize the current knowledge about the possible roles of p66Shc in different cancers.

Keywords: Cancer; cancer metabolism; p66Shc; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / physiology*
  • Cell Proliferation / physiology
  • Humans
  • Neoplasms / metabolism*
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism*
  • Shc Signaling Adaptor Proteins / metabolism*
  • Shc Signaling Adaptor Proteins / physiology
  • Signal Transduction
  • Src Homology 2 Domain-Containing, Transforming Protein 1


  • Reactive Oxygen Species
  • SHC1 protein, human
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1