LEP and cancer: Upregulation of TGF-β pathway induced transcriptional reprogramming of cancer stem cells, resulting in upregulated expression of leptin receptors in cancer stem cells and angiogenesis.284 As a result, benign tumor cells enhanced sensing and responding to circulatory leptin levels, and activated downstream PI3K-AKT-mammalian target of rapamycin (mTOR) pathway, leading to malignant transformation.284