Figure 2.

Adipose tissue signaling in breast cancer. (A) Leptin, a major adipocytokine released by adipose tissue binds to the leptin receptor and activates the JAK2-STAT3 pathway leading to proliferation and stemness of BC cells. Leptin transactivated HER2 receptor in absence of its ligand via JAK2, which leads to BC survival. Leptin also activates the ER receptor in absence of estrogens and, furthermore, inhibits its proteasomal degradation. (B) Aromatase secreted by adipose tissue converts androgens to estrogens leading to an increase in BC risk. (C) Visfatin increases the MAPK-ERK pathway through an unknown receptor thereby increasing BC proliferation. Activated MAPK also activates STAT3 signaling. (D) FABP4 expression is transcriptionally activated by the ERK-Ets1 pathway. Upon activation, FABP4 increases proliferation and migration of BC cells by nuclear accumulation of PPARγ and SREB2. Furthermore, FABP4 translocates to the cytoplasm where it binds to RA and, therefore, leads to cell differentiation. (E) Adiponectin increases the insulin signaling, glucose uptake, decreases glycogen synthesis and inhibits STAT3 and NFκB mediated signaling leading to the inhibition of BC survival and progression. (F) SFRP1 signaling through the integrin receptor inhibits pro-inflammatory cytokines, TGFβ and Wnt signaling, thereby inhibiting BC progression.