Fig. (3).

Proposed molecular mechanism whereby β2-m affects cancer growth and progression. The β2-m/HFE complex negatively regulates iron uptake through TFR complex and activates the PI3K/Akt, Raf/ERK, JAK/STAT3, cAMP/PKA/CREB, and HIF-1α signaling pathways, with increased cell growth/survival, angiogenesis, EMT and osteomimicry. β2-m activates both β2-m/PKA/CREB signaling and its convergent cell survival signaling network, PI3K/Akt and ERK, through VEGF-VEGFR signaling resulting in phosphorylation of Bad at Ser136 and Ser112. β2-m/PKA/CREB signaling also activates CREB-target gene expression including OC, OPN, BSP, cyclin A, and cyclin D leading to osteomimicry. β2-m/JAK/STAT3 signaling promotes the induction of EMT with increase of RANKL, N-cadherin, LIV-1 and vimentin expression and decrease of E-cadherin expression through Snail activation. Activated β2-m signaling also increases SREBP-1 transcription factor activity resulting in enhanced AR expression, lipogenesis, and ROS in prostate cancer cells.