MTDH (metadherin) is a multifunctional oncoprotein that promotes cancer progression through multiple mechanisms. Functionally, MTDH activates NF-κB transcription factor signaling 1 and regulates anchorage-independent growth in cancer cells [UniProt]. Its primary oncogenic roles include promoting tumor cell proliferation, invasion, angiogenesis, metastasis, and chemoresistance 2. Mechanistically, MTDH operates through protein-protein interactions, notably with SND1, where disrupting this complex suppresses breast cancer progression 3. MTDH also functions in regulatory networks; ADAR1 represses MTDH translation in an editing-dependent manner, and loss of this repression drives prostate cancer cell proliferation and invasion 4. Additionally, MTDH is regulated by the NORAD/miR-224-3p axis, which controls its expression and promotes chemoresistance in esophageal cancer 5. Clinically, MTDH overexpression is amplified in hepatocellular carcinoma and correlates with aggressive disease and poor prognosis across multiple cancer types 6. High MTDH expression significantly predicts distant metastasis, lymph node involvement, and reduced survival in breast, ovarian, and cervical cancers 7. MTDH serves as an independent prognostic biomarker and therapeutic target; combining MTDH inhibition with chemotherapy shows efficacy in preclinical models 36.