Ilkap, also known as integrin-linked kinase-associated phosphatase, is a serine/threonine phosphatase belonging to the protein phosphatase 2C family. It plays crucial roles in multiple cellular processes by regulating various signaling pathways. Ilkap is involved in the WNT signaling pathway, cell survival, apoptosis, and cell adhesion-related signaling. It is of great biological importance as it modulates key cellular functions that are essential for normal physiological processes and is implicated in disease development [1-5].

In hepatocellular carcinoma (HCC), Ilkap promotes cell metastasis by inhibiting β-catenin degradation and enhancing the WNT signaling pathway [1]. In severe hypoxia-induced apoptosis, Ilkap binds to and dephosphorylates hypoxia-inducible factor 1α (HIF-1α), which is essential for the apoptosis process [2]. In p53-wildtype glioblastoma cells, Ilkap is involved in radioresistance as its depletion sensitizes these cells to radiotherapy, and radiation-induced phosphorylation of DNA protein kinase (DNAPK) is dependent on Ilkap [3]. In prostate carcinoma cells, Ilkap inhibits the ILK-GSK3β signaling axis, modulates cell cycle progression, and suppresses anchorage-independent growth [4]. In endometrial tissues, lower Ilkap expression in eutopic and ectopic endometriosis tissue compared to control endometrium may facilitate the pathogenesis of endometriosis, and its level in ectopic endometrium might reflect disease severity [5].

In conclusion, Ilkap is essential in regulating multiple biological functions such as cell survival, apoptosis, and cell cycle progression. Its role in diseases like HCC, glioblastoma, and endometriosis is significant. Through various model-based studies, especially those showing loss-of-function effects, the understanding of Ilkap's functions in specific disease conditions has been enhanced, providing potential targets for disease treatment strategies.

References:

1. Zhang, Rui, Yuan, Jinglei, Liu, Shicheng, Zhou, Cefan, Tang, Jingfeng. 2024. ILKAP Promotes the Metastasis of Hepatocellular Carcinoma Cells by Inhibiting β-Catenin Degradation and Enhancing the WNT Signaling Pathway. In Advanced biology, 8, e2300117. doi:10.1002/adbi.202300117. https://pubmed.ncbi.nlm.nih.gov/38379270/

2. Liu, Tielong, Liu, Yonggang, Cao, Jiashi, Quan, Xinbao, Zou, Weiwei. 2018. ILKAP Binding to and Dephosphorylating HIF-1α is Essential for Apoptosis Induced by Severe Hypoxia. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 46, 2500-2507. doi:10.1159/000489656. https://pubmed.ncbi.nlm.nih.gov/29742494/

3. Hausmann, Christina, Temme, Achim, Cordes, Nils, Eke, Iris. . ILKAP, ILK and PINCH1 control cell survival of p53-wildtype glioblastoma cells after irradiation. In Oncotarget, 6, 34592-605. doi:10.18632/oncotarget.5423. https://pubmed.ncbi.nlm.nih.gov/26460618/

4. Kumar, Ashu S, Naruszewicz, Izabela, Wang, Ping, Leung-Hagesteijn, Chungyee, Hannigan, Gregory E. . ILKAP regulates ILK signaling and inhibits anchorage-independent growth. In Oncogene, 23, 3454-61. doi:. https://pubmed.ncbi.nlm.nih.gov/14990992/

5. Shao, Guangying, Zheng, Qiaomei, Xu, Xiaoxuan, Zhao, Jing, Liu, Peishu. 2015. Endometrial ILKAP expression among patients with endometriosis and its association with clinical characteristics. In International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 130, 23-6. doi:10.1016/j.ijgo.2015.01.015. https://pubmed.ncbi.nlm.nih.gov/25872452/