KRT7 promotes epithelial‑mesenchymal transition in ovarian cancer via the TGF‑β/Smad2/3 signaling pathway

Abstract

Keratin 7 (KRT7) is a member of the keratin gene family. KRT7 is abnormally expressed in various types of cancer and promotes the malignant progression of tumors. However, the role of KRT7 in ovarian cancer remains unclear. The present study aimed to validate the role of KRT7 in ovarian cancer progression. KRT7 expression levels in patients with ovarian cancer were analyzed using data obtained from the Human Protein Atlas and The Cancer Genome Atlas databases. KRT7 mRNA and protein expression levels were upregulated in ovarian cancer tissue compared with normal tissue. KRT7 expression was associated with the grading, staging and poor prognosis of ovarian cancer. The differentially expressed genes affected by KRT7 were primarily enriched in the functions of cell migration, cell adhesion and cell growth. In vitro studies, including a CCK8 assay, were used to detect cell proliferation. In addition, wound healing and transwell assays were performed to analyze cell migration. The results demonstrated that KRT7 overexpression was associated with increased proliferation, migration and epithelial-mesenchymal transition (EMT) of ovarian cancer cells, and the migration and EMT of ovarian cancers cells were decreased following knockdown with KRT7 small interfering RNA. In vivo , knockdown of KRT7 inhibited tumor growth of ovarian cancer. Furthermore, KRT7 regulated EMT in ovarian cancer via the TGF-β/Smad2/3 pathway, and regulated cell-matrix adhesion through integrin-β1-focal adhesion kinase signaling. These results suggest that KRT7 may be a potential molecular marker for prognosis prediction in patients with ovarian cancer.

A Keratin 7 and E-Cadherin Signature Is Highly Predictive of Tubo-Ovarian High-Grade Serous Carcinoma Prognosis

“…The literature is scarce and mixed regarding KRT7 regulation in cancer. It was observed in a recent publication that KRT7 overexpression in ovarian cancer cell lines was associated with increased proliferation, migration and EMT marker expression through the regulation of the TGF-β/Smad2/3 [ 23 ]. These results obtained on HGSC cell lines differ from our findings which show that KRT7 expression is not correlated with EMT markers in HGSC tissues and emphasizes the need to more fully characterize KRT7 functions in HGSC progression.…”

“…KRT7, KRT18, KRT19 protein expression in tumors were reported to predict prognosis in several cancer types [ 18 , 19 , 20 , 21 , 22 ]. However, despite reported functions of KRTs in tumor progression, relatively little is known about their value as prognostic markers in the context of HGSC [ 17 , 23 , 24 , 25 ]. Interestingly, we previously showed that KRT7 and KRT19 mRNA were elevated in OC compared to borderline tumors [ 26 ].…”

FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer

“…KRT5 is found in a population of basally located CD44 + stem-like cells in the FTE, for which its population is expanded in serous cancer samples [ 227 ]. KRT7 upregulates integrin β1-FAK signaling and matrix metalloproteinase expression, promoting cell matrix adhesion [ 241 ] and extracellular matrix degradation [ 228 ], respectively. The homeobox protein DLX-1 is a mediator in TGF-β1/SMAD4 signaling in ovarian cancer [ 224 ], which promotes EMT and cell stemness phenotypes [ 242 ].…”

A Prognostic Model Based on Immune-Related Long Non-Coding RNAs for Patients With Epithelial Ovarian Cancer

“…Among the 6-lncRNA signature, studies have found that KRT7-AS can promote tumor cell proliferation and migration, and KRT7 may promote epithelial-to-mesenchymal transition (EMT) of OC through TGFβ/Smad2/3 signaling pathway [28][29][30]. In our study, USP30-AS1 was regarded as a tumor suppressor factor.…”