Nolc1, also known as Nucleolar and coiled-body phosphoprotein 1, is a nucleolar protein. It is responsible for nucleolus construction and ribosomal RNA (rRNA) synthesis, and acts as a chaperone shuttling between the nucleolus and cytoplasm. Nolc1 participates in multiple cellular life activities such as ribosome biosynthesis, DNA replication, transcription regulation, RNA processing, cell cycle regulation, apoptosis, and cell regeneration [1].

In cancer research, Nolc1 knockdown suppresses prostate cancer progressions by reducing AKT phosphorylation and β-catenin accumulation, indicating its role in promoting prostate cancer progression [2]. The Pten-NOLC1 fusion gene promotes cancers involving MET and EGFR signalings, acting as a driver for human cancers [3]. In endometrial cancer, NOLC1 is highly expressed in paclitaxel-resistant cells, and the SPOP/NOLC1/B4GALT1 signaling axis enhances paclitaxel resistance by inducing O-dysglycosylation [4]. In epithelial ovarian cancer, circ-NOLC1, which is derived from Nolc1, promotes tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression [5]. In colorectal cancer, high expression of NOLC1 is an independent prognostic factor for survival, enhancing cell proliferation and migration [6]. In esophageal carcinoma, NOLC1 overexpression is associated with poor prognosis, and knockdown of NOLC1 inhibits the PI3K-AKT pathway to improve the prognosis [8]. However, in thyroid cancer, Nolc1 is identified as a tumor suppressor gene [7].

In conclusion, Nolc1 is crucial for various cellular functions, especially in ribosome-related processes. Through gene-knockdown or fusion-gene models in cancer research, its role in promoting or suppressing different cancers has been revealed. Understanding Nolc1 provides new perspectives for cancer diagnosis and therapeutic target selection.

References:

1. Zhai, Fengguang, Wang, Jie, Luo, Xia, Ye, Meng, Jin, Xiaofeng. 2023. Roles of NOLC1 in cancers and viral infection. In Journal of cancer research and clinical oncology, 149, 10593-10608. doi:10.1007/s00432-023-04934-5. https://pubmed.ncbi.nlm.nih.gov/37296317/

2. Kim, Wansoo, Yeo, Dong-Yeop, Choi, Seong-Kyoon, Park, Jin-Kyu, Park, Song. 2022. NOLC1 knockdown suppresses prostate cancer progressions by reducing AKT phosphorylation and β-catenin accumulation. In Biochemical and biophysical research communications, 635, 99-107. doi:10.1016/j.bbrc.2022.10.038. https://pubmed.ncbi.nlm.nih.gov/36265288/

3. Luo, Jian-Hua, Liu, Silvia, Tao, Junyan, Tseng, George, Yu, Yan-Ping. 2020. Pten-NOLC1 fusion promotes cancers involving MET and EGFR signalings. In Oncogene, 40, 1064-1076. doi:10.1038/s41388-020-01582-8. https://pubmed.ncbi.nlm.nih.gov/33323972/

4. Zhai, Fengguang, Li, Yuxuan, Zheng, Jingfei, Ye, Meng, Jin, Xiaofeng. 2025. SPOP/NOLC1/B4GALT1 signaling axis enhances paclitaxel resistance in endometrial cancer by inducing O-dysglycosylation. In Oncogene, , . doi:10.1038/s41388-025-03347-7. https://pubmed.ncbi.nlm.nih.gov/40097806/

5. Chen, Shuo, Wu, Wu, Li, Qian-Hui, Wei, Xiao-Qing, Zhao, Yang. 2021. Circ-NOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression. In Cell death discovery, 7, 22. doi:10.1038/s41420-020-00381-0. https://pubmed.ncbi.nlm.nih.gov/33483472/

6. Sun, Zhiwei, Zhang, Qianshi, Lv, Jinjuan, Zuo, Yun-Fei, Ren, Shuang-Yi. 2023. High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. In Journal of cancer research and clinical oncology, 149, 15697-15712. doi:10.1007/s00432-023-05297-7. https://pubmed.ncbi.nlm.nih.gov/37670166/

7. Zhai, Fengguang, Li, Yuxuan, Luo, Xia, Jin, Xiaofeng, Ye, Meng. 2024. NOLC1 was identified as a tumor suppressor gene in thyroid cancer and correlated with prognosis by bioinformatics. In American journal of cancer research, 14, 2055-2071. doi:10.62347/IYVV7581. https://pubmed.ncbi.nlm.nih.gov/38859850/

8. Kong, Fanguo, Shang, Yansheng, Diao, Xingyuan, Huang, Jiaguo, Liu, Hui. 2021. Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma. In Journal of oncology, 2021, 9944132. doi:10.1155/2021/9944132. https://pubmed.ncbi.nlm.nih.gov/34046062/