ING1, an inhibitor of growth gene, is a chromatin-targeting subunit of the Sin3a histone deacetylase (HDAC) complex. It has a crucial role in regulating gene expression by altering chromatin structure. ING1 is involved in multiple biological processes such as cell growth control, senescence, apoptosis, chromatin remodeling, and DNA repair, and is considered a type II tumor suppressor gene [2,3,4,5,6,7].

Knockdown of ING1 in cell-based studies increases the expression of EMT-related drivers like Twist1, Zeb 1&2, Snai1, Bmi1, and TSHZ1, promoting epithelial-to-mesenchymal transition (EMT) and cell motility. Conversely, ING1 expression promotes epithelial cell morphology and inhibits cell motility [1]. ING1 knockout mice spontaneously develop tumors, specifically B cell lymphomas, establishing its tumor-suppressor status [2]. In breast cancer, reduced ING1 levels promote metastasis both in vitro and in vivo, and there is an inverse relationship between ING1 and Twist1 levels in breast cancer samples [1,8].

In conclusion, ING1 is a multifaceted tumor suppressor gene. Through model-based research, especially gene knockout mouse models, its role in inhibiting tumorigenesis, EMT, and metastasis has been revealed. These findings emphasize the importance of ING1 in cancer-related research, providing potential therapeutic targets for breast cancer and other malignancies.

References:

1. Yang, Yang, Ma, Biao, Djamshidi, Mahbod, Zheng, Jianhua, Riabowol, Karl. 2023. ING1 inhibits Twist1 expression to block EMT and is antagonized by the HDAC inhibitor vorinostat. In European journal of cell biology, 102, 151341. doi:10.1016/j.ejcb.2023.151341. https://pubmed.ncbi.nlm.nih.gov/37459799/

2. Guérillon, Claire, Larrieu, Delphine, Pedeux, Rémy. 2013. ING1 and ING2: multifaceted tumor suppressor genes. In Cellular and molecular life sciences : CMLS, 70, 3753-72. doi:10.1007/s00018-013-1270-z. https://pubmed.ncbi.nlm.nih.gov/23412501/

3. Rusu, Alexandra D, Cornhill, Zoe E, Coutiño, Brenda Canales, Rahman, Ruman, Georgiou, Marios. 2021. CG7379 and ING1 suppress cancer cell invasion by maintaining cell-cell junction integrity. In Open biology, 11, 210077. doi:10.1098/rsob.210077. https://pubmed.ncbi.nlm.nih.gov/34493070/

4. Rajarajacholan, Uma Karthika, Thalappilly, Subhash, Riabowol, Karl. . ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization. In Nucleic acids research, 45, 1776-1792. doi:10.1093/nar/gkw1161. https://pubmed.ncbi.nlm.nih.gov/27903908/

5. Cheung, K J, Li, G. . The tumor suppressor ING1: structure and function. In Experimental cell research, 268, 1-6. doi:. https://pubmed.ncbi.nlm.nih.gov/11461112/

6. Feng, Xiaolan, Hara, Yasuo, Riabowol, KarlT. . Different HATS of the ING1 gene family. In Trends in cell biology, 12, 532-8. doi:. https://pubmed.ncbi.nlm.nih.gov/12446115/

7. Bose, P, Thakur, S, Thalappilly, S, Kim, S W, Riabowol, K. 2013. ING1 induces apoptosis through direct effects at the mitochondria. In Cell death & disease, 4, e788. doi:10.1038/cddis.2013.321. https://pubmed.ncbi.nlm.nih.gov/24008732/

8. Thakur, Satbir, Singla, Arvind K, Chen, Jie, Jirik, Frank, Riabowol, Karl. . Reduced ING1 levels in breast cancer promotes metastasis. In Oncotarget, 5, 4244-56. doi:. https://pubmed.ncbi.nlm.nih.gov/24962136/