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Cellular signals integrate cell cycle and metabolic control in cancer

Chareeporn Akekawatchai1, Sarawut Jitrapakdee2

  • 1Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand; Thammasat University Research Unit in Diagnostic Molecular Biology of Chronic Diseases related to Cancer (DMB-CDC), Pathumthani, Thailand.

Advances in Protein Chemistry and Structural Biology
|April 15, 2023
PubMed

Insights

Growth factors (GFs) can drive cell proliferation by activating receptor tyrosine kinases (RTKs). Cell cycle regulators fine-tune cellular metabolism to support tumor growth, with imbalances potentially leading to apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Metabolic Regulation

Background:

  • Growth factors (GFs) promote cell growth, differentiation, and survival.
  • Aberrant GF/receptor tyrosine kinase (RTK) signaling can lead to oncogenic transformation.
  • GF/RTK signaling influences major pathways like Ras/Erk and PI3K/Akt, driving cell cycle progression.

Purpose of the Study:

  • To explore the intricate relationship between cell cycle regulation and metabolic reprogramming in cancer.
  • To elucidate the role of specific cell cycle regulators in modulating metabolic pathways.
  • To understand how metabolic imbalances during the cell cycle contribute to cancer progression and cell fate.

Main Methods:

  • Review of accumulating evidence linking GF/RTK signaling to cell cycle progression.
  • Analysis of the role of key cell cycle regulators (cyclins, CDKs, APC/C-Cdh1) in metabolic control.
  • Investigation of post-translational modifications and transcriptional regulation of metabolic enzymes by cell cycle regulators.

Main Results:

  • GF signaling enables quiescent cells to re-enter the cell cycle and proliferate.
  • Tumor cells exhibit significant metabolic changes during proliferation to meet biomass and energy demands.
  • Cell cycle regulators (cyclin D, B, Cdk2, 4, 6, APC/C-Cdh1) critically control metabolic pathways.
  • Metabolic enzyme activity is regulated via post-translational mechanisms or transcriptional control by cell cycle regulators.
  • Precise metabolic pathway activation supports biosynthetic precursor availability during proliferation.

Conclusions:

  • Cell cycle regulators orchestrate metabolic reprogramming essential for tumor cell proliferation.
  • Imbalances in cellular metabolism during specific cell cycle phases can trigger cell cycle arrest and apoptosis.
  • Targeting the interplay between cell cycle and metabolism presents a potential therapeutic strategy in oncology.
Keywords:
ApoptosisCancerCell cycleGrowth factorsMetabolismReceptor tyrosine kinase

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