LZTFL1, also known as Leucine Zipper Transcription Factor-like 1, is a gene with significant biological importance. It functions as a tumor suppressor in multiple cancers and is involved in pathways like the ubiquitin-proteosome pathway, leptin signaling, and regulation of ciliary signaling. Genetic models such as KO mouse models are valuable for studying its functions [1,2,3,4,5,6].

In cancer research, LZTFL1 deletion is frequent in various cancers. In clear cell renal cell carcinoma (ccRCC), its down-regulation is linked to poor outcomes, and it inhibits kidney tumor cell growth by destabilizing AKT through the ZNRF1-mediated ubiquitin proteosome pathway [1]. In hepatocellular carcinoma (HCC), decreased LZTFL1 expression is associated with tumor stage and metastasis, and its overexpression inhibits cell proliferation, migration, and invasion [2]. In lung cancer, down-regulation is related to recurrence and poor survival, and it may inhibit tumorigenesis by maintaining epithelial cell differentiation [3]. In gastric cancer, it suppresses cell migration and invasion by regulating β-catenin nuclear translocation [6]. In a global Lztfl1-deficient mouse model, obesity was observed due to leptin-resistance in the hypothalamus, as inactivation of Lztfl1 abolished phosphorylation of Stat3 in the LepRb signaling pathway [5].

In conclusion, LZTFL1 plays essential roles as a tumor suppressor in multiple cancer types and in regulating energy homeostasis through the leptin signaling pathway in the hypothalamus. The use of KO mouse models has been crucial in revealing these functions, providing insights into potential therapeutic strategies for cancer and obesity-related diseases.

References:

1. Lu, Jun, Fu, Liang-Min, Cao, Yun, Liu, Zhi-Ping, Luo, Jun-Hang. 2023. LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway. In Oncogene, 42, 1543-1557. doi:10.1038/s41388-023-02666-x. https://pubmed.ncbi.nlm.nih.gov/36966254/

2. Li, Shasha, Li, Jingjing, Yu, Zujiang. 2019. Tumor suppressive functions of LZTFL1 in hepatocellular carcinoma. In OncoTargets and therapy, 12, 5537-5544. doi:10.2147/OTT.S196925. https://pubmed.ncbi.nlm.nih.gov/31371991/

3. Wei, Q, Chen, Z-H, Wang, L, Luo, J-H, Liu, Z P. 2015. LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells. In Oncogene, 35, 2655-63. doi:10.1038/onc.2015.328. https://pubmed.ncbi.nlm.nih.gov/26364604/

4. Sun, Wei-Yue, Xue, Bin, Liu, Yan-Xia, Wu, Mingfu, Fan, Zhen-Chuan. . Chlamydomonas LZTFL1 mediates phototaxis via controlling BBSome recruitment to the basal body and its reassembly at the ciliary tip. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2101590118. https://pubmed.ncbi.nlm.nih.gov/34446551/

5. Wei, Qun, Gu, Yi-Feng, Zhang, Qing-Jun, Liu, Tiemin, Liu, Zhi-Ping. . Lztfl1/BBS17 controls energy homeostasis by regulating the leptin signaling in the hypothalamic neurons. In Journal of molecular cell biology, 10, 402-410. doi:10.1093/jmcb/mjy022. https://pubmed.ncbi.nlm.nih.gov/30423168/

6. Wang, Linbo, Guo, Jufeng, Wang, Qinchuan, Wei, Qun, Liu, Zhi-Ping. 2014. LZTFL1 suppresses gastric cancer cell migration and invasion through regulating nuclear translocation of β-catenin. In Journal of cancer research and clinical oncology, 140, 1997-2008. doi:10.1007/s00432-014-1753-9. https://pubmed.ncbi.nlm.nih.gov/25005785/