Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer

Abstract

Despite good responses to first-line treatment with platinum-based combination chemotherapy, most ovarian cancer patients will relapse and eventually develop platinum-resistant disease with poor prognosis. Although reports suggest that integrin-linked kinase (ILK) is a potential target for ovarian cancer treatment, identification of ILK downstream effectors has not been fully explored. The purpose of this study was to investigate the molecular and biological effects of targeting ILK in cisplatin-resistant ovarian cancer. Western blot analysis showed that phosphorylation levels of ILK were higher in cisplatin-resistant compared with cisplatin-sensitive ovarian cancer cells. Further immunohistochemical analysis of ovarian cancer patient samples showed a significant increase in phosphorylated ILK levels in the tumor tissue when compared to normal ovarian epithelium. Targeting ILK by small-interfering RNA (siRNA) treatment reduced cisplatin-resistant cell growth and invasion ability, and increased apoptosis. Differential gene expression analysis by RNA sequencing (RNA-Seq) upon ILK-siRNA transfection followed by Ingenuity Pathway Analysis (IPA) and survival analysis using the Kaplan–Meier plotter database identified multiple target genes involved in cell growth, apoptosis, invasion, and metastasis, including several non-coding RNAs. Taken together, results from this study support ILK as an attractive target for ovarian cancer and provide potential ILK downstream effectors with prognostic and therapeutic value.

A novel tailored immune gene pairs signature for overall survival prediction in lower-grade gliomas

“…External and internal verification were used to evaluate the predictive ability of the signature. Two KM survival curves for OS were first compared using the log-rank test ( p < 0.05) [14] , while the 1-, 3-, and 5-year time-dependent receiver operating characteristic (ROC) curves were visualized in the training and testing cohorts [15] . The risk score coupled with five clinical factors (age, sex, WHO grade, IDH mutation status, and 1p/19q codeletion status) was tested for independent assessment using univariate and multivariate Cox regression analyses.…”

Integrin-linked kinase affects the sensitivity of esophageal squamous cell carcinoma cells to chemotherapy with cisplatin via the Wnt/beta-catenin signaling pathway

“…Moreover, due to its involvement in the regulation of a variety of cellular biological processes, it is associated with the occurrence, development, invasion, and metastases of malignant tumors, and, as such, affects the prognosis of these tumors [ 24 ]. It has been reported that ILK gene knockout can inhibit the invasion and metastasis of Renal Cell Carcinoma and breast cancer [ 11 , 25 ], and is also an attractive target for the treatment of ovarian cancer [ 26 ]. Previous experimental results derived by the authors’ team showed that the downregulation of ILK inhibited the proliferation and migration of ESCC cells, suggesting that ILK may play an important role in the progression of ESCC.…”

GTW inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer via ILK/AKT/GSK3β/Slug Signalling Pathway

“…As the upstream regulatory molecule of AKT, ILK is a key factor that regulates the interaction between extracellular matrix and cells by phosphorylating of its downstream substrates AKT and GSK3β 42 . ILK has significant effects on the development and progression of human carcinoma 20 , 43 , 44 , including promoting the metastatic behaviour of EOC cells 45 . It has been reported that ILK facilitates cancer cell migration, invasion and drug-resistance by regulating EMT processes 46 .…”