Mtdh, also known as AEG-1 and LYRIC, is a 582-amino-acid transmembrane protein encoded by a gene located at chromosome 8q22. It is distributed in the cytoplasm, peri-nuclear region, nucleus, nucleolus, and endoplasmic reticulum. Mtdh is a multifunctional mediator involved in multiple signaling pathways such as PI3K/Akt, NF-κB, Wnt/β-catenin, and MAPK, playing a crucial role in carcinogenesis, including cancer cell proliferation, invasion, angiogenesis, metastasis, and chemoresistance [3,4].

Genetic ablation of Mtdh in mice has shown to inhibit breast cancer development by disrupting its interaction with SND1, which is essential for breast cancer progression in established tumors [1]. Also, the MTDH-SND1 complex has been found to suppress antitumor T-cell responses in breast cancer by reducing tumor antigen presentation and inhibiting T-cell infiltration and activation. Pharmacological disruption of this complex enhanced immune surveillance and sensitivity to anti-PD-1 therapy in preclinical models of metastatic breast cancer [2].

In conclusion, Mtdh is a key gene in multiple biological processes, especially in cancer progression. The use of gene-knockout mouse models has revealed its role in breast cancer, highlighting its potential as a therapeutic target for metastatic breast cancer. The MTDH-SND1 complex is a particularly important aspect, and disrupting this interaction shows promise in enhancing cancer treatment efficacy [1,2].

References:

1. Shen, Minhong, Wei, Yong, Kim, Hahn, Shao, Zhi-Ming, Kang, Yibin. 2021. Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis. In Nature cancer, 3, 43-59. doi:10.1038/s43018-021-00279-5. https://pubmed.ncbi.nlm.nih.gov/35121987/

2. Shen, Minhong, Smith, Heath A, Wei, Yong, Shao, Zhi-Ming, Kang, Yibin. 2021. Pharmacological disruption of the MTDH-SND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer. In Nature cancer, 3, 60-74. doi:10.1038/s43018-021-00280-y. https://pubmed.ncbi.nlm.nih.gov/35121988/

3. Shi, Xue, Wang, Xin. 2015. The role of MTDH/AEG-1 in the progression of cancer. In International journal of clinical and experimental medicine, 8, 4795-807. doi:. https://pubmed.ncbi.nlm.nih.gov/26131054/

4. Abdel Ghafar, Muhammad T, Soliman, Nema A. 2021. Metadherin (AEG-1/MTDH/LYRIC) expression: Significance in malignancy and crucial role in colorectal cancer. In Advances in clinical chemistry, 106, 235-280. doi:10.1016/bs.acc.2021.09.007. https://pubmed.ncbi.nlm.nih.gov/35152973/