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Metabostemness in cancer: Linking metaboloepigenetics and mitophagy in remodeling cancer stem cells

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Abstract

Cancer stem cells (CSCs) are rare populations of malignant cells with stem cell-like features of self-renewal, uninterrupted differentiation, tumorigenicity, and resistance to conventional therapeutic agents, and these cells have a decisive role in treatment failure and tumor relapse. The self-renewal potential of CSCs with atypical activation of developmental signaling pathways involves the maintenance of stemness to support cancer progression. The acquisition of stemness in CSCs has been accomplished through genetic and epigenetic rewiring following the metabolic switch. In this context, “metabostemness” denotes the metabolic parameters that essentially govern the epitranscriptional gene reprogramming mechanism to dedifferentiate tumor cells into CSCs. Several metabolites often referred to as oncometabolites can directly remodel chromatin structure and thereby influence the operation of epitranscriptional circuits. This integrated metaboloepigenetic dimension of CSCs favors the differentiated cells to move in dedifferentiated macrostates. Some metabolic events might perform as early drivers of epitranscriptional reprogramming; however, subsequent metabolic hits may govern the retention of stemness properties in the tumor mass. Interestingly, selective removal of mitochondria through autophagy can promote metabolic plasticity and alter metabolic states during differentiation and dedifferentiation. In this connection, novel metabostemness-specific drugs can be generated as potential cancer therapeutics to target the metaboloepigenetic circuitry to eliminate CSCs.

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Acknowledgments

We apologize to the authors for any fundamental studies that were omitted due to space limitations. Research support was partly provided by the Department of Biotechnology [BT/PR23304/MED/30/1823/2017], Ministry of Science and Technology, Government of India.

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Research support was provided by the Department of Biotechnology [BT/PR23304/MED/30/1823/2017], Ministry of Science and Technology, Government of India.

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  1. Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, Odisha, 769008, India

    Prajna Paramita Naik, Prakash Priyadarshi Praharaj, Chandra Sekhar Bhol & Sujit Kumar Bhutia

  2. P.G. Department Zoology, Vikram Deb Autonomous College, Jeypore, Koraput, Odisha, India

    Prajna Paramita Naik, Swagatika Panigrahi & Ratnakar Parida

  3. Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia

    Shankargouda Patil

  4. Department of Surgical Oncology, HCG Panda Cancer Hopspital, Cuttack, Odisha, India

    NML Manjunath

  5. Department of Natural Products, National Institute of Pharmaceutical Research and Education (NIPER), Kolkata, India

    Dipanjan Ghosh

  6. Epigenetics and Cancer Research Laboratory, Department of Life Science, National Institute of Technology Rourkela, Sundergarh, Odisha, India

    Samir Kumar Patra

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PPN, PPP, CSB and SKB conceived the review. PPN, SP, RP, PPP CSB and SKB wrote the review, centralized and integrated comments from co-authors, and prepared the figures and tables. SP, MN, DG, SKP and SKB corrected the manuscript and provided valuable input to obtain a consensus view.

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Naik, P.P., Panigrahi, S., Parida, R. et al. Metabostemness in cancer: Linking metaboloepigenetics and mitophagy in remodeling cancer stem cells . Stem Cell Rev and Rep 18, 198–213 (2022). https://doi.org/10.1007/s12015-021-10216-9

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