Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.

Interplay Between Thiamine and p53/p21 Axes Affects Antiproliferative Action of Cisplatin in Lung Adenocarcinoma Cells by Changing Metabolism of 2-Oxoglutarate/Glutamate

“…Remarkably, the shape of attached A549 p21– cells demonstrate elongation absent in the A549 WT cells ( Figure 1G ). The morphological change is reminiscent of epithelial-mesenchymal transition, known to reduce cisplatin sensitivity ( Deng et al, 2019 ; Bahar et al, 2020 ; Brum et al, 2020 ; Chen et al, 2020 ; Siraj et al, 2020 ), which is also observed in our experiments ( Figure 1E ).…”

Overexpression of the pro‐protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling

“…Sphere forming assay was performed as described previously [ 40 ]. Briefly, PTC cells (500 per well) were plated on Corning 24‐well ultra‐low attachment plates (Corning Inc., Kennebunk, ME, USA) grown in serum‐free DMEM‐F12 (ATCC) supplemented with B27 (Gibco, Grand Island, NY, USA), 20 ng·mL −1 epidermal growth factor (Sigma‐Aldrich, Saint Louis, MO, USA), 0.4% bovine serum albumin (Sigma‐Aldrich, Milwaukee, WI, USA) and 4 μg·mL −1 insulin (Sigma‐Aldrich, Saint Louis, MO, USA).…”

PRMT5 activates KLF5 by methylation to facilitate lung cancer

“…Kruppel‐like factor 5, also known as KLF5, is a transcription factor that is expressed in various tissues and plays crucial roles in cell proliferation, differentiation and survival. 4 However, abnormal expression of KLF5 has been observed in many different types of cancer, including breast, 5 prostate, 6 colon, 7 ovarian cancer, 8 liver 9 and lung. 10 In some cases, KLF5 overexpression has been linked to unfavourable outcomes such as increased tumour growth, poor prognosis and resistance to chemotherapy.…”