MTDH (AEG-1) is involved inHIF-1alpha mediatedangiogenesis. MTDH also interacts withSND1 and involved inRNA-induced silencing complex (RISC) and plays very important role in RISC andmiRNA functions.[8][9] MTDH has been shown to interact with spliceosome proteins in the cell nucleus and regulate the process of alternative splicing.[10]
MTDH induces an oncogene called Late SV40 factor (LSF/TFCP2) which is involved inthymidylate synthase (TS) induction and DNA biosynthesis synthesis.[11] Late SV40 factor (LSF/TFCP2) enhances angiogenesis by transcriptionally up-regulating matrix metalloproteinase-9 (MMP9).[12]
Elevated expression of MTDH, which is overexpressed in more than 40% of breast cancers, is associated with poor clinical outcomes. MTDH has a dual role in promotingmetastatic seeding and enhancing chemoresistance. MTDH is therefore a potential therapeutic target for enhancingchemotherapy and reducing metastasis.[14][15][16][17]
MTDH has been shown to be overexpressed inprostate cancer, where there is a shift towards a more cytoplasmic localisation, signalling a poor prognosis.[18][19] In the nucleus of prostate cancer cells, MTDH has been shown to affect alternative splicing of genes such as CD44, which may also be associated with prostate cancer progression.[10]
LSF/TFCP2 plays a multifaceted role in chemo resistance, EMT, allergic response, inflammation andAlzheimer's disease.[20]
MTDH controls many hallmarks of oncogenes and cancer. MTDH/AEG-1 induceshepato steatosis in mouse liver.[21] MTDH knockdown by artificialmicroRNA interference functions as a potentialtumor suppressor in breast cancer.[22] Astrocyte elevated gene-1/MTDH undergoespalmitoylation in normal and abnormal cell physiology.[23] Biomaterial titanium substrata with microgrooves can alter MTDH expression in human primary cells.[24]
^Sutherland HG, Lam YW, Briers S, Lamond AI, Bickmore WA (March 2004). "3D3/lyric: a novel transmembrane protein of the endoplasmic reticulum and nuclear envelope, which is also present in the nucleolus".Experimental Cell Research.294 (1):94–105.doi:10.1016/j.yexcr.2003.11.020.PMID14980505.
^Lee MH, Kang JH, Lee SW (April 2012). "The significance of differential expression of genes and proteins in human primary cells caused by microgrooved biomaterial substrata".Biomaterials.33 (11):3216–34.doi:10.1016/j.biomaterials.2012.01.034.PMID22285466.
^Neeli PK, Gollavilli PN, Mallappa S, Hari SG, Kotamraju S (March 2020). "A novel metadherinΔ7 splice variant enhances triple negative breast cancer aggressiveness by modulating mitochondrial function via NFĸB-SIRT3 axis".Oncogene.39 (10):2088–2102.doi:10.1038/s41388-019-1126-6.PMID31806873.S2CID208648747.
van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. (January 2002). "Gene expression profiling predicts clinical outcome of breast cancer".Nature.415 (6871):530–6.doi:10.1038/415530a.hdl:1874/15552.PMID11823860.S2CID4369266.
Sutherland HG, Lam YW, Briers S, Lamond AI, Bickmore WA (March 2004). "3D3/lyric: a novel transmembrane protein of the endoplasmic reticulum and nuclear envelope, which is also present in the nucleolus".Experimental Cell Research.294 (1):94–105.doi:10.1016/j.yexcr.2003.11.020.PMID14980505.
