Application of the Yamanaka Transcription Factors Oct4, Sox2, Klf4, and c-Myc from the Laboratory to the Clinic

Genes (Basel). 2023 Aug 26;14(9):1697. doi: 10.3390/genes14091697.

Abstract

The transcription factors Oct4, Sox2, Klf4, and c-Myc enable the reprogramming of somatic cells into induced pluripotent cells. Reprogramming generates newly differentiated cells for potential therapies in cancer, neurodegenerative diseases, and rejuvenation processes. In cancer therapies, these transcription factors lead to a reduction in the size and aggressiveness of certain tumors, such as sarcomas, and in neurodegenerative diseases, they enable the production of dopaminergic cells in Parkinson's disease, the replacement of affected neuronal cells in olivopontocerebellar atrophy, and the regeneration of the optic nerve. However, there are limitations, such as an increased risk of cancer development when using Klf4 and c-Myc and the occurrence of abnormal dyskinesias in the medium term, possibly generated by the uncontrolled growth of differentiated dopaminergic cells and the impairment of the survival of the new cells. Therefore, the Yamanaka transcription factors have shown therapeutic potential through cell reprogramming for some carcinomas, neurodegenerative diseases, and rejuvenation. However, the limitations found in the studies require further investigation before the use of these transcription factors in humans.

Keywords: Klf4; Oct4; Sox2; c-Myc; cancer; cell- and tissue-based therapy; induced pluripotent stem cells; neurodegenerative diseases; rejuvenation.

Publication types

  • Review

MeSH terms

  • Aggression
  • Carcinoma*
  • Cell Differentiation / genetics
  • Humans
  • Kruppel-Like Factor 4
  • Laboratories
  • Octamer Transcription Factor-3 / genetics
  • Proto-Oncogene Proteins c-myc
  • SOXB1 Transcription Factors
  • Sarcoma*

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Kruppel-Like Factor 4
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Proto-Oncogene Proteins c-myc

Grants and funding

The Universidad de La Sabana financed the publication of the article, project MED-96-2008.