Stmn1, also known as stathmin 1, is a microtubule-destabilizing phosphoprotein. It plays a crucial role in regulating cellular microtubule dynamics, which is essential for cell cycle progression, mitosis, signal transduction, and cell migration [4,5,6]. It is involved in multiple signaling pathways such as the MAPK signaling pathway [2]. Stmn1 is of great biological importance as its dysregulation is associated with various diseases, especially malignancies. Genetic models, like KO/CKO mouse models, can be valuable in studying its functions.

In triple-negative breast cancer (TNBC), protein phosphatase 1 regulatory subunit 14B (PPP1R14B) stabilizes STMN1, promoting cancer progression and paclitaxel resistance. Deficiency of PPP1R14B's tumor-suppressive effects could be partially rescued by wild-type STMN1 but not phosphorylation-deficient STMN1, indicating STMN1's importance in this context [1]. In non-small cell lung cancer (NSCLC), STMN1 promotes metastasis through microtubule-dependent and non-microtubule-dependent mechanisms. Knockdown of STMN1 could potentially inhibit NSCLC metastasis [3]. In acute promyelocytic leukemia cells, knockdown of STMN1 decreased autonomous cell growth [4].

In conclusion, Stmn1 is a key regulator of microtubule dynamics with significant implications in cancer. Studies using KO/CKO mouse models (implied by the functional studies in these diseases) could further clarify its role in tumorigenesis and metastasis in TNBC, NSCLC, and leukemia, potentially providing new therapeutic targets for these malignancies.

References:

1. Liao, Li, Zhang, Yin-Ling, Deng, Ling, Shao, Zhi-Min, Li, Da-Qiang. . Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer. In Cancer research, 83, 471-484. doi:10.1158/0008-5472.CAN-22-2709. https://pubmed.ncbi.nlm.nih.gov/36484700/

2. Zhang, Yubao, Wei, Shijie, Zhang, Qinxiang, Zhang, Yue, Sun, Changgang. 2024. Paris saponin VII inhibits triple-negative breast cancer by targeting the MEK/ERK/STMN1 signaling axis. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 130, 155746. doi:10.1016/j.phymed.2024.155746. https://pubmed.ncbi.nlm.nih.gov/38763012/

3. Zeng, Lizhong, Lyu, Xin, Yuan, Jingyan, Li, Wei, Yang, Shuanying. 2024. STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways. In International journal of biological sciences, 20, 1509-1527. doi:10.7150/ijbs.84738. https://pubmed.ncbi.nlm.nih.gov/38385074/

4. Vicari, Hugo Passos, Coelho-Silva, Juan Luiz, Pereira-Martins, Diego A, Traina, Fabiola, Machado-Neto, João Agostinho. 2021. STMN1 is highly expressed and contributes to clonogenicity in acute promyelocytic leukemia cells. In Investigational new drugs, 40, 438-452. doi:10.1007/s10637-021-01197-0. https://pubmed.ncbi.nlm.nih.gov/34837603/

5. Dou, Yun-De, Zhao, Han, Huang, Tao, Liu, Hong-Bin, Chen, Zi-Jiang. 2016. STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells. In Scientific reports, 6, 26691. doi:10.1038/srep26691. https://pubmed.ncbi.nlm.nih.gov/27270953/

6. Li, Xingyu, Wang, Lulu, Li, Tiejun, Qian, Li, Cao, Xiaolei. 2015. STMN1 overexpression correlates with biological behavior in human cutaneous squamous cell carcinoma. In Pathology, research and practice, 211, 816-23. doi:10.1016/j.prp.2015.07.009. https://pubmed.ncbi.nlm.nih.gov/26235036/