The TCL1 function revisited focusing on metabolic requirements of stemness

Maria Teresa Fiorenza, Alessandro Rava

Research output: Contribution to journalReview articlepeer-review

Abstract

The oncogenic ability of the T-cell leukemia/lymphoma 1 gene, TCL1, has captured the attention in the field of prolymphocytic T-cell and B-cell chronic leukemias for more than two decades. However, the finding that TCL1 is also expressed in totipotent cells of the mouse preimplantation embryos and that it is among the 10 genes, including the transcription factors Nanog, Oct4, Sox2, Tbx3, and Esrrb, that are required for maintaining the mitotic self-renewal state of embryonic stem cells, raises a great interest. In this review, we highlight newly acquired evidence pinpointing TCL1 as a crucial regulator of metabolic pathways that dictate somatic cell reprogramming toward pluripotency. In our opinion, this feature provides a relevant hint for reframing the role that this factor plays at early stages of mammalian embryo development and in tumorigenesis. Hence, the TCL1-dependent enhancement of serine/threonine AKT/PKB kinase activity favoring cell proliferation appears to be associated to the promotion of glucose transport and activation of glycolytic pathways. This is also consistent with the TCL1 ability to suppress mitochondrial biogenesis and oxygen consumption, downplaying the contribution of oxidative phosphorylation to energy metabolism. It thus appears that TCL1 masters the direction of energy metabolism toward the glycolytic pathway to meet a critical metabolic requirement that goes beyond the mere ATP production. For instance, the synthesis of glycolytic intermediates that are required for DNA synthesis likely represents the most pressing cellular need for both cleavage-stage embryos and rapidly proliferating tumor cells.

Original languageEnglish
Pages (from-to)3055-3063
Number of pages9
JournalCell Cycle
Volume18
Issue number22
DOIs
Publication statusPublished - Nov 17 2019

Keywords

  • cell proliferation/differentiation
  • Embryonic totipotent/pluripotent stem cells
  • energy metabolism shift

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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