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Yoshioka K, Atsumi Y, Nakagama H, et al. Development of cancer-initiating cells and immortalized cells with genomic instability. World J Stem Cells. 2015;7(2):483-9doi: 10.4252/wjsc.v7.i2.483.
Yoshioka, K., Atsumi, Y., Nakagama, H., & Teraoka, H. (2015). Development of cancer-initiating cells and immortalized cells with genomic instability. World journal of stem cells, 7(2), 483-9. https://doi.org/10.4252/wjsc.v7.i2.483
Yoshioka, Ken-Ichi, et al. "Development of cancer-initiating cells and immortalized cells with genomic instability." World journal of stem cells vol. 7,2 (2015): 483-9. doi: https://doi.org/10.4252/wjsc.v7.i2.483
Yoshioka K, Atsumi Y, Nakagama H, Teraoka H. Development of cancer-initiating cells and immortalized cells with genomic instability. World J Stem Cells. 2015 Mar 26;7(2):483-9. doi: 10.4252/wjsc.v7.i2.483. PMID: 25815132; PMCID: PMC4369504.
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World J Stem Cells. 2015 Mar 26;7(2):483-9. doi: 10.4252/wjsc.v7.i2.483.

Development of cancer-initiating cells and immortalized cells with genomic instability.

World journal of stem cells

Ken-Ichi Yoshioka, Yuko Atsumi, Hitoshi Nakagama, Hirobumi Teraoka

Affiliations

  1. Ken-ichi Yoshioka, Yuko Atsumi, Hitoshi Nakagama, Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

PMID: 25815132 PMCID: PMC4369504 DOI: 10.4252/wjsc.v7.i2.483

Abstract

Cancers that develop after middle age usually exhibit genomic instability and multiple mutations. This is in direct contrast to pediatric tumors that usually develop as a result of specific chromosomal translocations and epigenetic aberrations. The development of genomic instability is associated with mutations that contribute to cellular immortalization and transformation. Cancer occurs when cancer-initiating cells (CICs), also called cancer stem cells, develop as a result of these mutations. In this paper, we explore how CICs develop as a result of genomic instability, including looking at which cancer suppression mechanisms are abrogated. A recent in vitro study revealed the existence of a CIC induction pathway in differentiating stem cells. Under aberrant differentiation conditions, cells become senescent and develop genomic instabilities that lead to the development of CICs. The resulting CICs contain a mutation in the alternative reading frame of CDKN2A (ARF)/p53 module, i.e., in either ARF or p53. We summarize recently established knowledge of CIC development and cellular immortality, explore the role of the ARF/p53 module in protecting cells from transformation, and describe a risk factor for genomic destabilization that increases during the process of normal cell growth and differentiation and is associated with the downregulation of histone H2AX to levels representative of growth arrest in normal cells.

Keywords: ARF/p53 module; Cancer stem cells; Cancer-initiating cells; Differentiation; Genomic instability; H2AX

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