Regulation of cancer stem cells in triple negative breast cancer.

Norman Fultang,Bela Peethambaran,Madhuparna Chakraborty

doi:10.20517/cdr.2020.106

Norman Fultang, Bela Peethambaran + Show 1 more

Open Access

https://doi.org/10.20517/cdr.2020.106

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Abstract

Triple Negative Breast Cancer (TNBC) is the most lethal subtype of breast cancer. Despite the successes of emerging targeted therapies, relapse, recurrence, and therapy failure rates in TNBC significantly outpace other subtypes of breast cancer. Mounting evidence suggests accumulation of therapy resistant Cancer Stem Cell (CSC) populations within TNBCs contributes to poor clinical outcomes. These CSCs are enriched in TNBC compared to non-TNBC breast cancers. The mechanisms underlying CSC accumulation have been well-characterized and discussed in other reviews. In this review, we focus on TNBC-specific mechanisms that allow the expansion and activity of self-renewing CSCs. We highlight cellular signaling pathways and transcription factors, specifically enriched in TNBC over non-TNBC breast cancer, contributing to stemness. We also analyze publicly available single-cell RNA-seq data from basal breast cancer tumors to highlight the potential of emerging bioinformatic approaches in identifying novel drivers of stemness in TNBC and other cancers.

Highlights

Breast cancer remains the most commonly diagnosed cancer in women and the second leading cause of cancer-related deaths in women worldwide[1]
Several of the markers we identified in our analysis have not been described within the context of Cancer Stem Cell (CSC) or TNBC CSCs (TNBCSCs)
We provide an exhaustive summary of known regulatory mechanisms for CSCs in Triple Negative Breast Cancer (TNBC)

Summary

INTRODUCTION

Breast cancer remains the most commonly diagnosed cancer in women and the second leading cause of cancer-related deaths in women worldwide[1]. Pcdh: Protocadherin-7; Dcn: decorin; Plpp: phospholipid phosphatase 3; Creb3l1: CAMP responsive element binding protein 3 like 1; Hexa: hexosaminidase A; Ppic: peptidylprolyl isomerase C; Serpina3n: serine protease inhibitor A3N precursor; Mmp14-matrix metallopeptidase 14; Snhg: small nucleolar RNA host Gene 18; Vcan: versican; Ifitm: interferon induced transmembrane protein 2; Col4a1: collagen alpha-1(IV); Gstm: glutathione S-transferase mu 2; Serf: small EDRK-rich factor 2; Calu: calumenin; Marcks: myristoylated alanine rich protein kinase C substrate; Bmp-1 Bone morphogenetic protein-1; Selenof: selenoprotein F precursor; Itm2c: integral membrane protein 2C; Rrbp: ribosome-binding protein 1; Vasn: vasorin; col27a1: collagen alpha-1 (XXVII); Ugdh: UDP-glucose dehydrogenase; Il6st: interleukin 6 signal transducer; Ckap: cytoskeleton associated protein 4; Vat: vesicle amine transport 1; Lamc: laminin subunit gamma-1; Pdia: protein disulfide-isomerase A3; Cyth: cytohesin-3 have all been shown to play a role in regulating cell growth and pluripotency[18,199,200] Deregulations in these mechanisms, especially at loci of growth and pluripotency related genes, have been associated with tumorigenesis and stemness in several cancers[18,199,200,201].

CONCLUSION

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