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Role of c-Met/HGF Axis in Altered Cancer Metabolism

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Cancer Cell Metabolism: A Potential Target for Cancer Therapy

Abstract

c-Met (mesenchymal–epithelial transition factor) is a receptor tyrosine kinase that belongs to the Met family and is majorly expressed on the surfaces of epithelial cells. Hepatocyte growth factor (HGF) is the receptor specific to c-Met. HGF binding to c-Met leads to the initiation of series of cascade mediating wound healing and embryogenesis. However, in cancer cells, mutation in c-Met stimulates various downstream signalling pathways such as PI3K/AKT, Ras/MAPK, and JAK/STAT, causing aberrant c-Met/HGF axis activation and resulting in development and progression through migration, invasion, and metabolic reprogramming in cancer. c-Met/HGF axis modulates glucose metabolism in cancer by altering major enzymes and transporters such as hexokinase, phosphofructokinase, lactate dehydrogenase, and glucose transporters and shifts the reliance of cancer cells on glucose rather than oxidative phosphorylation even in the presence of oxygen (Warburg phenomena). In addition, c-Met/HGF axis modulates and interferes with other pathways such as pentose phosphate pathway, amino acid metabolism, and TCA cycle leading to its aggressive phenotypes. Therefore, understanding the association between c-Met/HGF axis and signalling pathways is critical and clinically important to develop therapeutic drugs. In this chapter, we discuss the molecular structure of HGF and c-Met and the mechanism through which this axis interacts and activates other signalling pathways involved in metabolic reprogramming of cancer cells.

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Change history

  • 13 March 2020

    The following late corrections have been carried out in the updated version of chapters 6 and 7:

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Acknowledgments

We sincerely thank all authors for their valuable inputs and carefully reading the manuscript.

Conflicts of interest: The authors declare no conflict of interest.

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Authors and Affiliations

  1. Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh (AUUP), Noida, Uttar Pradesh, India

    Vaishali Chandel, Sibi Raj & Dhruv Kumar

  2. Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA

    Ramesh Choudhari

  3. Shri B. M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapur, India

    Ramesh Choudhari

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  1. Vaishali Chandel
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  2. Sibi Raj
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  4. Dhruv Kumar
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Correspondence to Dhruv Kumar .

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  1. Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh (AUUP), Noida, Uttar Pradesh, India

    Dhruv Kumar

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Chandel, V., Raj, S., Choudhari, R., Kumar, D. (2020). Role of c-Met/HGF Axis in Altered Cancer Metabolism. In: Kumar, D. (eds) Cancer Cell Metabolism: A Potential Target for Cancer Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-15-1991-8_7

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