Llgl2, also known as lethal (2) giant larvae protein homolog 2, is a scaffolding protein that regulates the establishment of apical-basal polarity in epithelial cells. It is involved in asymmetric cell division, cell migration, and progenitor cells self-renewal. In zebrafish development, it regulates epidermal cell proliferation and migration as well as cortical F-actin formation [1].

In ovarian cancer, LLGL2 was found to inhibit cell migration and invasion in vitro and metastasis in vivo. Low expression of LLGL2 was associated with advanced stages, higher grades, and poor patient survival. Mechanistically, LLGL2 regulates cytoskeletal remodeling by interacting with ACTN1 without changing its protein and mRNA levels [1]. In ER+ breast cancer, LLGL2 is overexpressed and promotes cell proliferation under nutrient stress by regulating leucine uptake via a trimeric complex with SLC7A5 and YKT6 [2]. In hepatocellular carcinoma, LLGL2 is up-regulated, promoting cell proliferation, migration, and invasion through the PI3K/AKT signaling pathway by increasing calcium ion influx [3]. In endometrial cancer, LLGL2 expression is upregulated, promoting cell proliferation, migration, and invasion, potentially through activation of the Hedgehog signaling pathway [4].

In conclusion, LLGL2 has diverse functions in different tissues and diseases. Its role in regulating cell polarity, migration, and proliferation is crucial. Model-based research, especially in cancer, has revealed its potential as a biomarker and therapeutic target in diseases such as ovarian, breast, liver, and endometrial cancers [1,2,3,4].

References:

1. Gu, Qiu-Ying, Liu, Yue-Xi, Wang, Jin-Long, Li, Ruo-Nan, Linghu, Hua. 2023. LLGL2 Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via ACTN1. In Cancers, 15, . doi:10.3390/cancers15245880. https://pubmed.ncbi.nlm.nih.gov/38136424/

2. Saito, Yasuhiro, Li, Lewyn, Coyaud, Etienne, Brown, Myles, Muthuswamy, Senthil K. 2019. LLGL2 rescues nutrient stress by promoting leucine uptake in ER+ breast cancer. In Nature, 569, 275-279. doi:10.1038/s41586-019-1126-2. https://pubmed.ncbi.nlm.nih.gov/30996345/

3. Leng, Shusheng, Xie, Fei, Liu, Junyi, Quan, Guangqian, Wen, Tianfu. 2021. LLGL2 Increases Ca2+ Influx and Exerts Oncogenic Activities via PI3K/AKT Signaling Pathway in Hepatocellular Carcinoma. In Frontiers in oncology, 11, 683629. doi:10.3389/fonc.2021.683629. https://pubmed.ncbi.nlm.nih.gov/34178676/

4. Yang, Hua, Ji, Yuqing, Liu, Dong, Sun, Bei, Wang, Fang. 2024. LLGL2 targets the Hedgehog signaling pathway to influence malignant progression of endometrial cancer. In Cellular signalling, 127, 111553. doi:10.1016/j.cellsig.2024.111553. https://pubmed.ncbi.nlm.nih.gov/39647764/