The Role of Epithelial-to-Mesenchymal Plasticity in Ovarian Cancer Progression and Therapy Resistance

Abstract

Ovarian cancer is the most lethal of all gynecologic malignancies and the eighth leading cause of cancer-related deaths among women worldwide. The main reasons for this poor prognosis are late diagnosis; when the disease is already in an advanced stage, and the frequent development of resistance to current chemotherapeutic regimens. Growing evidence demonstrates that apart from its role in ovarian cancer progression, epithelial-to-mesenchymal transition (EMT) can promote chemotherapy resistance. In this review, we will highlight the contribution of EMT to the distinct steps of ovarian cancer progression. In addition, we will review the different types of ovarian cancer resistance to therapy with particular attention to EMT-mediated mechanisms such as cell fate transitions, enhancement of cancer cell survival, and upregulation of genes related to drug resistance. Preclinical studies of anti-EMT therapies have yielded promising results. However, before anti-EMT therapies can be effectively implemented in clinical trials, more research is needed to elucidate the mechanisms leading to EMT-induced therapy resistance.

Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

“…Briefly stating, EMT is a process when epithelial cells lose their signature characteristics like cell-cell adhesion to acquire a mesenchymal phenotype with migratory and invasive behavior [83]. Apart from its role in EOC metastasis, EMT can promote tumor initiation, stemness, and chemoresistance in EOC [84]. STAT proteins have been well documented to play a role in fostering EMT in several cancer entities [85][86][87].…”

Morin exerts anti-metastatic, anti-proliferative and anti-adhesive effect in ovarian cancer cells: an in vitro studies

“…Typical biomarkers for EMT are cell-surface proteins, cytoskeletal markers, and extracellular proteins. Downregulation of genes encoding, among others, E-cadherin, occludin, desmoplakin, keratin (type I cytoskeletal 19), caveolin-2, and fibroblast growth factorbinding protein 1 is associated with the 3 type EMT [10][11][12]. On the other hand, up-regulated during EMT in cancer are genes encoding, among others, N-cadherin, α5β1 integrin, αVβ6 integrin, vimentin, β-catenin, caldesmon, moesin, α1(I) collagen, α1(III) collagen, fibronectin, matrix metalloproteinase-9, matrix metalloproteinase-2, stromelysin-1, metalloproteinase inhibitor 1, and versican core protein [11,13].…”

“…EMT involves epigenetic alterations to chromatin modifications at both the DNA and protein level. Transcription factors important for regulation of EMT belong to the three main families such as TWIST (TWIST1 and TWIST2), SNAI (Snail and Slug), and ZEB (ZEB1 and ZEB2) involve various histone-modifying complexes to chromatin, mediating epigenetic silencing of genes [10,11,14].…”

Nanodrug Delivery Systems for the Treatment of Ovarian Cancer

“…Globally, ovarian cancer (OC) is a lethal condition that accounts for millions of deaths annually in females, making this condition a major health issue [1][2][3][4][5][6]. In the last five-year survey, statistics reflected approximately 21.9 million new patients clinically diagnosed with OC on a yearly basis, with 14,270 deaths predicted in the United States every year [7].…”

“…In the last five-year survey, statistics reflected approximately 21.9 million new patients clinically diagnosed with OC on a yearly basis, with 14,270 deaths predicted in the United States every year [7]. According to the World Health Organization (WHO), OC is one of the most lethal genital malignancies in females in developing countries, with this asymptomatic disease exacerbated by lack of early diagnostic strategies and access to expensive chemotherapeutic drugs [1]. In Africa (South Africa), the Cancer Council of Southern Africa (CANSA) confirmed more than 500 cases of OC [8].…”