Abstract
Obesity and its related complications have been the pressing disease pandemic affecting the developed world. It is well-established that the direct consequence of obesity in the cardiovascular system resulting in many diseases. However, its implications in carcinogenesis, cancer treatment and one’s anti-tumour immunity are gradually unfolding. To understand how fat cells can affect these, one needs to explore how the fat cell affects epithelial and immune cells. To this end, we explore the way how the adipocytes, via its production of adipokines, influence these cells, resulting in early epithelial cell transformation into cancer cells and influencing anti-tumour immunity once the cancer is established. In order to simplify our discussion, we focus this review on breast cancer. We propose that to have an effective therapy for cancer treatment, we need to intervene at the adipokine interaction with epithelial cells, cancer cells, and immune cells. In this review we also decipher the potential therapeutic targets in controlling carcinogenesis and disease progression.
Highlights
Obesity is traditionally viewed as the chronic and excessive growth of adipose tissue
We propose that to have an effective therapy for cancer treatment, we need to intervene at the adipokine interaction with epithelial cells, cancer cells, and immune cells
The molecular mechanisms underlying the relationship between obesity and breast carcinogenesis involves adipokines, oestrogens, insulin and inflammatory cytokines
Summary
Obesity is traditionally viewed as the chronic and excessive growth of adipose tissue. Several leptin dependent signalling kinases, including ERK-p90-RSK and Akt, which phosphorylate GSK3β, along with the increase of MTA1 expression, regulate the function of this Wnt pathway to promote EMT in BC [108] Another complex signalling crosstalk between leptin, Notch and IL-1 seems to be an important driver of leptin-induced oncogenic action, proinflammatory effect and pro-angiogenic state [109]. There is a very complex network of immune cells and molecules along with signalling pathways that can be affected by the concentration of APN present, more data needs to be obtained before coming to a conclusion about the therapeutic effects of APN on BC Whereas for leptin, it promotes systemic inflammation via TNF-α and IL-6 [111,162], and induces HIF1α and VEGF which can propagate cancer survival, proliferation and migration [163][164]. When one is relying on antitumour immunity to mount adequate response to cancer, avoiding the use of APN and perhaps introducing leptin either endogenously by increasing BMI or exogenously by pharmacological means may be an attractive approach in ensuring successful treatment of advance cancer
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