Inflammation and ER stress differentially regulate STAMP2 expression and localization in adipocytes.

Background: Chronic ER stress and dysfunction is a hallmark of obesity and a critical contributor to metaflammation, abnormal hormone action and altered substrate metabolism in metabolic tissues, such as liver and adipocytes. Lack of STAMP2 in lean mice induces inflammation and insulin resistance on a regular diet, and it is dysregulated in the adipose tissue of obese mice and humans. We hypothesized that the regulation of STAMP2 is disrupted by ER stress.

STAMP2 is required for human adipose-derived stem cell differentiation and adipocyte-facilitated prostate cancer growth .

Six Transmembrane Protein of Prostate 2 (STAMP2) has been implicated in both prostate cancer (PCa) and metabolic disease. STAMP2 has unique anti-inflammatory and pro-metabolic properties in mouse adipose tissue, but there is limited information on its role in human metabolic tissues. Using human adipose-derived stem cells (ASCs), we report that STAMP2 expression is dramatically upregulated during adipogenesis.

Analysis of androgen-induced increase in lipid accumulation in prostate cancer cells.

Increased metabolic activity is a hallmark of proliferating cancer cells. One common deregulated metabolic pathway in prostate cancer is de novo lipogenesis which is highly increased in prostate cancer and is linked to poor prognosis and metastasis. Male sex hormones play an essential role in prostate cancer growth and have been shown to increase the expression and activity of several lipogenic factors, such as fatty acid synthase (FASN) and sterol regulatory element-binding proteins (SREBPs), leading to accumulation of neutral lipids in prostate cancer cells.

STAMPs at the crossroads of cancer and nutrition.

Prostate cancer is the most diagnosed noncutaneous cancer among men in Western developed countries. Nutrition and environmental factors play a major role in the onset of the disease, but the molecular details for the contribution of each factor is elusive. In an effort to better understand the basic biology of prostate cancer, we identified a new protein family that is named the 6 trans-membrane protein of prostate (STAMP) that appear to have important functions in prostate cancer.

Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis.

Metabolic and inflammatory pathways crosstalk at many levels, and, while required for homeostasis, interaction between these pathways can also lead to metabolic dysregulation under conditions of chronic stress. Thus, we hypothesized that mechanisms might exist to prevent overt inflammatory responses during physiological fluctuations in nutrients or under nutrient-rich conditions, and we identified the six-transmembrane protein STAMP2 as a critical modulator of this integrated response system of inflammation and metabolism in adipocytes. Lack of STAMP2 in adipocytes results in aberrant inflammatory responses to both nutrients and acute inflammatory stimuli.