Affiliations: Physiology and Biophysics, Robert Wood Johnson Medical
School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA | Department of Cell and Developmental Biology, Rutgers
University, New Brunswick, NJ, USA | Department of Biochemistry, Robert Wood Johnson
Medical School, University of Medicine and Dentistry of New Jersey, Piscataway,
NJ, USA
Note: [] Corresponding author: Dr. Emine Ercikan Abali, Department of
Biochemistry, 675 Hoes Lane, Research Tower, Room 527, Piscataway, NJ 08854,
USA. Tel.: +1 732 235 3911; Fax: +1 732 235 8181; E-mail: abaliem@umdnj.edu
Abstract: In the past several decades obesity has become an increasingly
problematic public health concern in developed countries. The strong
correlation between high birth weights, obesity in adolescence and cancer is
now evident. However, the molecular mechanism connecting obesity and cancer has
yet to be elucidated. Here we review current literature investigating this
relationship at both hormonal and biochemical levels. We also explore recent
publications for novel cancer therapies that target pathways in which cancer
manipulates host metabolism. The hormone leptin, which is upregulated in obese
individuals, signals satiety and has been shown to play a role in signaling
pathways promoting metastasis in a number of different cancers. Furthermore,
leptin receptors are increased in some cancers and as a result these cells
begin to utilize aerobic glycolysis for energy production as opposed to
oxidative phosphorylation. Tumorigenic cells use alternative splicing to select
for specific metabolic enzymes, which then serve as metabolic tools to promote
tumor proliferation. A hypoxic environment can lead to the activation of
AMP-activated protein kinase (AMPK), which in turn activates glycolytic
machinery. It also upregulates transcription factors that promote tumor
angiogenesis and allow sustained tumor growth. A more detailed understanding of
metabolic aberrations due to obesity and their contribution to the onset of
cancer is critical for the development of new therapies in the fight against
both diseases.
