PRKAA1 and breast cancer: However, a number of resistance mechanisms have been proposed for biguanides including mtDNA mutations in genes that encode for Complex 1.24 Mutations in LKB1, a kinase upstream of AMPK, have been reported in MDA-MB-231 cells and to mediate sensitivity to metformin.25,26 See Fig. 5 summarising our model with regard to the effect of metformin on lipid metabolism on breast cancer cells.