• mM metformin inhibits mTOR signaling as reflected by a reduction in phosphorylated Akt and mTOR.• Metformin inhibits activation of mTOR through down-regulation of the Sp1, Sp3 and Sp4 transcription factors transcription and IGF-1R.• Conclusion: Metformin targets genes and signaling pathways important for tumor migration, invasion, proliferation and survival. Here, SP4 is linked to neoplasm.