Cell Cycle Regulators' Role in Cancer Cell Metabolism

Leal-Esteban, L.C. and Fajas, L. (2020, February). “Cell cycle regulators in cancer cell
metabolism”.
The article, “Cell cycle regulators in cancer cell metabolism” written by Lucia Leal-
Esteban and Lluis Fajas attempts to emphasize the function of major cell cycle regulators
in cancer cell metabolic adaptability and how this control might be used to treat cancer
patients.

Auto radiographic investigations were used to show that DNA synthesis happens at a
certain time throughout the cell division process. Interphase and Mitosis, or M phase, are
the two primary stages in which eukaryotic cells divide their cell cycle. The article indicates
that proliferating cells have a high energy demand, and their metabolism needs to adjust
to meet these demands. The so-called Warburg effect, is the first and most studied
metabolic adaptation in cancer cells. Importantly, the extensive metabolic abnormalities
seen commonly in cancer are a characteristic of the disease, and they have aided in the
development of anticancer therapy options that target the disrupted metabolic pathways.

The article discusses in detail the important role of CDKs in cell cycle progression. They
belong to a group of Serine/Threonine Kinases that create active heterodimeric
complexes after binding to cyclins. Cyclin Dependent Kinases, are a type of enzyme that
uses signals to activate cell cycle mechanisms. CDKs are activated by creating
complexes with cyclins, another type of cell cycle regulating proteins that are only present
for a limited time. In cancer cells, the loss of certain inhibitory mechanisms leads to the
accumulation of cyclins and CDKs, which can lead to cell cycle progression and
proliferation. Human cancers are often caused by homozygous mutations in the
INK4a/APRF/INK4b gene which regulates the expression of oncogenic signals. Genetic
mutations that cause the dysfunction or lack of one or more regulatory proteins at cell
cycle checkpoints might cause the "molecular switch" to be permanently turned on,
allowing uncontrolled cell multiplication and eventually tumor growth.
The authors states that every cellular action, such as cell development, proliferation,
or senescence, requires precise energy and metabolic pathway adjustments. These
changes suggest that those cellular activities must coordinate with external signals and
energy balance regulation. A detailed look at the reprogramming energy metabolism
should be included in understanding the signaling pathways that are deregulated during
cancer progression. Indeed, alterations in cellular metabolism should be viewed as an
interdependent factor, emphasizing the significance of metabolic regulation in cell
survival.
The authors indicate how distinct regulators of cell cycle progression affect genes and
enzymes involved in DNA synthesis and cell division throughout the cell cycle. Cumulative
evidence was shown to indicate that cell cycle regulators can target proteins that directly
affect metabolic processes in addition to their canonical substrates. These findings show
a link between those signaling pathways and cell growth and proliferation, as well as the
regulation of a number of metabolic enzymes, implying that the crosstalk between cellular
metabolism and cell-cycle and cell division processes is a coordinated response to
external stimuli facilitated by oncogenes or cell cycle regulators. Altogether, this evidence
indicates that cell cycle components and metabolic processes are inextricably linked.
However, despite significant progress in understanding the complexities of energy
utilization during the cell cycle, a full model that incorporates all of the discoveries reported
in many cell lines, organs, and organisms remain unclear.
The authors discuss in detail the recent advances in CDK inhibitors as a potential
pharmacological therapy for cancer growth. Initially, the discovery of pan-CDK inhibitors
allowed researchers to gain a better knowledge of their many targets and mechanisms of
action. However, CDK inhibitors monotherapy may not be helpful enough in certain types
of cancer, according to the research.

This article review has evaluated the article “Cell cycle regulators in cancer cell
metabolism” by Lucia Leal-Esteban and Lluis Fajas. The arguments in the article show
the role of cell cycle regulators in cancer cell metabolism with concrete evidence and
information. However, many fundamental questions, remain unanswered. Particularly,
how similar are the requirements for energy generation to different tissues or even
different organisms. Overall, the article gave a substantial amount of data and it is clearly
evident that the authors widely studied the canonical roles of the cell cycle regulators
although some points in the article remain unclear and difficult to understand. These
points weaken the author’s arguments.
References:

Leal-Esteban, L.C. and Fajas, L. (2020, February). “Cell cycle regulators in cancer cell
metabolism”. Retrieved from
https://www.sciencedirect.com/science/article/pii/S0925443920300600?via%3Dihub#ab
0010
Collins, K., Jacks T., and Pavletich N.P. (1994). “The cell cycle and cancer”. Retrieved
from https://www.pnas.org/content/94/7/2776
Ding, L., et al. (2020). “The Roles of Cyclin-Dependent Kinases in Cell-Cycle
Progression and Therapeutic Strategies in Human Breast Cancer”. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139603/