SOX4, a member of the group C subfamily of SOX transcription factors, is an essential developmental transcription factor. It regulates stemness, differentiation, progenitor development, and is involved in multiple pathways such as PI3K, Wnt, and TGFβ signaling [2,3]. It plays a significant role in various biological processes and is associated with multiple diseases.

In triple-negative breast cancer (TNBC), inactivation of SOX4 in tumor cells increases the expression of genes in immune pathways, and targeting the integrin αvβ6-TGFβ-SOX4 pathway may offer therapeutic opportunities [1]. In colorectal cancer, METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis [4]. In castration-resistant prostate cancer, targeting the SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation [5]. In neuroblastoma cells, SOX4 mediates ATRA-induced differentiation, with its overexpression inhibiting cell proliferation [6].

In conclusion, SOX4 is crucial in development and disease. Through gene-knockout or conditional-knockout mouse models and other functional studies, its role in cancer progression, metastasis, and cell differentiation has been revealed. Understanding SOX4's functions in these disease areas provides potential therapeutic targets and insights into disease mechanisms.

References:

1. Bagati, Archis, Kumar, Sushil, Jiang, Peng, Liu, X Shirley, Wucherpfennig, Kai W. 2020. Integrin αvβ6-TGFβ-SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer. In Cancer cell, 39, 54-67.e9. doi:10.1016/j.ccell.2020.12.001. https://pubmed.ncbi.nlm.nih.gov/33385331/

2. Moreno, Carlos S. 2019. SOX4: The unappreciated oncogene. In Seminars in cancer biology, 67, 57-64. doi:10.1016/j.semcancer.2019.08.027. https://pubmed.ncbi.nlm.nih.gov/31445218/

3. Hanieh, Hamza, Ahmed, Emad A, Vishnubalaji, Radhakrishnan, Alajez, Nehad M. 2019. SOX4: Epigenetic regulation and role in tumorigenesis. In Seminars in cancer biology, 67, 91-104. doi:10.1016/j.semcancer.2019.06.022. https://pubmed.ncbi.nlm.nih.gov/31271889/

4. Chen, Xiaoxiang, Xu, Mu, Xu, Xueni, Sun, Huilin, Wang, Shukui. 2020. METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. In Molecular cancer, 19, 106. doi:10.1186/s12943-020-01220-7. https://pubmed.ncbi.nlm.nih.gov/32552762/

5. Jing, Nan, Tao, Zhenkeke, Du, Xinxing, Dong, Baijun, Fang, Yu-Xiang. 2024. Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer. In Biology direct, 19, 56. doi:10.1186/s13062-024-00500-2. https://pubmed.ncbi.nlm.nih.gov/39014441/

6. Zhang, Dongyang, Gong, Baocheng, Zhao, Qiang, Tan, Xiaolin, Hua, Zhongyan. 2022. SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells. In Cancers, 14, . doi:10.3390/cancers14225642. https://pubmed.ncbi.nlm.nih.gov/36428735/