Characteristics of Cancer Stem Cells and Their Potential Role in Endometrial Cancer

Abstract

Endometrial cancer is one of most common types of gynaecological tumours in developing countries. It has been suggested that cancer stem cells play an important role in the development of endometrial cancer. These are a subset of highly tumorigenic cells with similar features to normal stem cells (unlimited proliferation, multi-potential differentiation, self-renewal, aggressiveness, invasion, recurrence, and chemo- and endocrine therapy resistance). Wnt/β-catenin, Hedghog, and Notch1 are the most frequently activated pathways in endometrial cancer stem cells. The presence of cancer stem cells is associated with the resistance to chemotherapy caused by different mechanisms. Various markers, including CD24, CD40, CD44, CD9, CD133, and CD 166, have been identified on the surface of these cells. A higher expression of such markers translates into enhanced tumorigenicity. However, there is no strong evidence showing that any of these identified markers can be used as the universal marker for endometrial cancer stem cells. Growing data from genomic and proteomic profiling shed some light on the understanding of the molecular basis of cancers in humans and the role of cancer stem cells. However, there is much left to discover. Therefore, more studies are needed to fully uncover their functional mechanisms in order to prevent the development and recurrence of cancer, as well as to enhance treatment effectiveness.

Keywords: CD117; CD133; CD44; cancer stem cells; endometrial cancer.

Figure 1

The summary of potential therapeutic targets. Abbreviations: ALDH, aldehyde dehydrogenase; AMPK, 5′AMP-activated protein kinase; BMI-1, B-lymphoma Mo-MLV insertion region 1; CD44, cluster of differentiation 44; EGF, epidermal growth factor; GLI, transcription factor GLI; GRP48, G Protein Coupled Receptor 48; GSK3β, glycogen synthase kinase-3β; HER2, human epidermal growth factor receptor 2; Hh, hedgehog signalling pathway; Hoxa5, homeobox A5; IL-1,-6, interleukin-1,-6; LRP5/6, Low-density lipoprotein receptor-related protein 5; MMP-7, Matrix Metalloprotease-7; mTOR, mammalian target of rapamycin; MYC, MYC MYC transcription factor; NF-κB, nuclear factor κB; PD-1, programmed death receptor-1; PD-L1, programmed death receptor-1 ligand; PI3K, phosphatidylinositol 3-kinases; PTCH1, receptor called Patched 1; SMO, signal transducer called Smoothened; SMYD3, SET and MYND domain containing 3; SUFU, cytoplasmic protein; TCF1, T cell factor 1; TNF-α, tumour necrosis factor α; TNFR, tumour necrosis factor receptor; Wnt, Wnt signalling pathway.

Figure 2

Clinical trials of new endometrial cancer therapies. AIs, aromatase inhibitors; EC, endometrial carcinoma; EEC, early endometrial carcinoma; GnRHa, gonadotropin-releasing hormone analogue; IMGN853, mirvetuximab soravtansine; MA, megestrol acetate; MPA, medroxyprogesterone acetate.