Fig. 7

A schematic diagram to show SHP/RAS/ERK pathway and γ-T3 targets in mammosphere cells. In mammosphere cells, γ-T3 targets both SHP1 and SHP2 to down regulate RAS/ERK pathway and subsequently leads to the cell death in mammospheres. For SHP1, γ-T3 promotes its protein production to down-regulate Ras/ERK pathways. γ-T3 through down-regulating the protein level and phosphorylation of SHP2 reduces the interaction with associated proteins such as GRB2 and GAB2, leading to activation of the RAS/ERK pathway. It is postulated that in the nucleus, the double action of down-regulation of ERK interferes with the transcription factors C-myc and Cyd ensuring normal cell cycles (green arrows) and the anti-apoptosis factors Bcl-XL and Spred subsequently cause cell cycle arrest and apoptosis of the mammosphere cells (Red arrows)