Abstract
Obesity is currently affecting more than 40% of the Americans, and if it progresses with this rate, soon one out of two Americans will be obese. Obesity is an important risk factor for several disorders including cardiovascular disease, the first cause of death in the United States. Cancer follows as the second deadliest disease, and a link between obesity and cancer has been suggested. However, it is very hard to establish an exact connection between obesity and cancers due to the multifactorial nature of obesity. Hypercholesterolemia is a comorbidity of obesity and also linked to several cancers. Recently a cholesterol metabolite 27-hydroxycholesterol (27HC) was found to be an endogenous selective estrogen receptor modulator (SERM), which opened new doors toward several interesting studies on the role of this molecule in biological disorders. It is speculated that 27HC might be the missing link in the obesity and cancer chain. Here, we explored the effects of 27-hydroxycholesterol on obesity and cancers with a focus on the SERM capacity of 27HC.
Highlights
Cancer is the second cause of death after heart disease in the United States, projecting to lead to more than 600,000 deaths in 2020 [1]
The discovery of 27HC as an endogenous selective estrogen receptor modulator (SERM) led to extensive studies on the potential roles of this molecule in many diseases including cancers
Adipose tissues form a major part of the breast tissue, thereby breast tumors are surrounded by adipose tissues
Summary
Cancer is the second cause of death after heart disease in the United States, projecting to lead to more than 600,000 deaths in 2020 [1]. Nelson et al demonstrated that 27HC increased the breast cancer tumor growth in an ER-dependent manner in an immune-competent mouse mammary tumor virus-polyoma middle T-antigen (MMTV-PyMT) model, which develops spontaneous ERα-positive mammary adenocarcinomas that metastasize to the lung [23] They showed that 27HC increased the epithelial to mesenchymal transition marker expressions in a similar manner to the effects of other LXR ligands, which suggests that probably not all of the impacts of 27HC on breast cancer are through ER [23]. All these works suggest a potential role of 27HC in endocrine therapy resistance of breast cancer, yet it needs extensive studies before any certain conclusions can be drawn. All these studies showed a potentially critical role of 27HC in many cancers, and further research is warranted to elucidate the exact effects of 27HC in various cancers
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