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Research Perspective|Volume 11, Issue 3|pp 1065—1068

Hallmarks of the cancer cell of origin: Comparisons with “energetic” cancer stem cells (e-CSCs)

Federica Sotgia1, Marco Fiorillo1,2, Michael P. Lisanti1
  • 1Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester, M5 4WT, United Kingdom
  • 2The Department of Pharmacy, Health and Nutritional Sciences, The University of Calabria, Cosenza, Italy
Received: January 16, 2019Accepted: February 7, 2019Published: February 13, 2019
https://doi.org/10.18632/aging.101822

Copyright: © 2019 Sotgia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Here, we discuss the expected hallmark(s) of the cancer cell of origin and how this may be related to a new tumor cell phenotype, namely “energetic” cancer stem cells (e-CSCs). e-CSCs show many features that would be characteristic of the cancer cell of origin, including the over-expression of p21-WAF (CDKN1A), a key marker of senescence. It is tempting to speculate that the cancer cell of origin and e-CSCs are closely related entities. e-CSCs possess a hybrid phenotype, sharing key hallmarks of senescence, “stemness” and cancer. e-CSCs are hyper-proliferative and have elevated mitochondrial metabolism, with an NRF2-mediated anti-oxidant response signature, including glutaredoxin (GLRX) and ALDH3A1 over-expression, possibly related to their escape from senescence. Finally, in e-CSCs, BCAS1 (Breast carcinoma-amplified sequence-1) protein expression was up-regulated by >100-fold. BCAS1 is a candidate oncogene associated with “stemness” and aggressive oncogenic behavior, such as Tamoxifen resistance.