Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Mar 21;23(6):3412.
doi: 10.3390/ijms23063412.

Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?

Constanze Banz-Jansen  1   2 , Laureen P Helweg  2   3 , Barbara Kaltschmidt  2   3   4
Affiliations
Review

Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?

Constanze Banz-Jansen et al. Int J Mol Sci. .

Abstract

Endometrial cancer is one of the most common malignant diseases in women worldwide, with an incidence of 5.9%. Thus, it is the most frequent cancer of the female genital tract, with more than 34,000 women dying, in Europe and North America alone. Endometrial Cancer Stem Cells (CSC) might be drivers of carcinogenesis as well as metastatic and recurrent disease. Therefore, targeting CSCs is of high interest to improve prognosis of patients suffering of advanced or recurrent endometrial cancer. This review describes the current evidence of molecular mechanisms in endometrial CSCs with special emphasis on MYC and NF-κB signaling as well as mitochondrial metabolism. Furthermore, the current status of immunotherapy targeting PD-1 and PD-L1 in endometrial cancer cells and CSCs is elucidated. The outlined findings encourage novel therapies that target signaling pathways in endometrial CSCs as well as immunotherapy as a promising therapeutic approach in the treatment of endometrial cancer to impede cancer progression and prevent recurrence.

Keywords: MYC; NF-κB; PD-1; PD-L1; cancer stem cells; endometrial cancer; endometrial cancer stem cells; mitochondria.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Activated Signaling Pathways in Endometrial Cancer Stem Cells and possible Target Sites. Activated Wnt/β-Catenin Signaling leads to the expression of stemness genes Oct-4, Sox-2 and Nanog as well as activates NF-κB. NF-κB is also activated by the PI3K/AKT/mTOR pathway, whose activation is mediated by tyrosine receptor kinases like HER2 and leads to the expression of genes like c-Myc and Snail. Another receptor contributing to cancer stem cell characteristics is Notch. Possible target sites affecting these pathways as well as stemness, resistance and invasiveness of CSCs are pictured in the black boxes. PI3K = phosphatidylinositol 3-kinase; HER2 = human epidermal growth factor receptor 2; EGF = epidermal growth factor; ECM = extracellular matrix; mTOR = mammalian target of rapamycin.
Figure 2
Figure 2
Endometrial Cancer Stem Cell as a therapeutical Target for Cancer Therapy.
See this image and copyright information in PMC

References

    1. Torre L.A., Bray F., Siegel R.L., Ferlay J., Lortet-Tieulent J., Jemal A. Global cancer statistics, 2012. CA Cancer J. Clin. 2015;65:87–108. doi: 10.3322/caac.21262. - DOI - PubMed
    1. Renehan A.G., Tyson M., Egger M., Heller R.F., Zwahlen M. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–578. doi: 10.1016/S0140-6736(08)60269-X. - DOI - PubMed
    1. Nevadunsky N.S., van Arsdale A., Strickler H.D., Moadel A., Kaur G., Levitt J., Girda E., Goldfinger M., Goldberg G.L., Einstein M.H. Obesity and age at diagnosis of endometrial cancer. Obstet. Gynecol. 2014;124:300–306. doi: 10.1097/AOG.0000000000000381. - DOI - PubMed
    1. Furau A., Tit D.M., Furau C., Bungau S., Furau G., Toma M.M., Cirstoveanu C.G., Petre I., Todor D.-S., Romosan R.S., et al. Analysis of the Impact of Comorbidities on Endometrial Lesions Using the Charlson Comorbidity Index in Western Romania. Medicina. 2021;57:945. doi: 10.3390/medicina57090945. - DOI - PMC - PubMed
    1. Tataru A.-L., Furau G., Afilon J., Ionescu C., Dimitriu M., Bratu O.G., Tit D.M., Bungau S., Furau C. The Situation of Cervical Cancers in the Context of Female Genital Cancer Clustering and Burden of Disease in Arad County, Romania. J. Clin. Med. 2019;8:96. doi: 10.3390/jcm8010096. - DOI - PMC - PubMed