Signaling pathways essential for triple-negative breast cancer stem-like cells

Abstract

Since the discovery of breast cancer stem cells (CSCs), a significant effort has been made to identify and characterize these cells. It is a generally believe that CSCs play an important role in cancer initiation, therapy resistance, and progression of triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor prognosis. Thus, therapies targeting these cells would be a valuable addition to standard treatments that primarily target more differentiated, rapidly dividing TNBC cells. Although several cell surface and intracellular proteins have been described as biomarkers for CSCs, none of these are specific to this population of cells. Recent research is moving toward cellular signaling pathways as targets and biomarkers for CSCs. The WNT pathway, the nuclear factor-kappa B (NF-κB) pathway, and the cholesterol biosynthesis pathway have recently been identified to play a key role in proliferation, survival, and differentiation of CSCs, including those of breast cancer. In this review, we assess recent findings related to these three pathways in breast CSC, with particular focus on TNBC CSCs, and discuss how targeting these pathways, in combination with current standard of care, might prove effective and improve the prognosis of TNBC patients.

CHFR regulates chemoresistance in triple-negative breast cancer through destabilizing ZEB1

“…Until now, therapies targeting specific molecular targets have rarely produced meaningful clinical improvements in the outcome of TNBC patients, and conventional chemotherapy is still the standard of treatment [35]. TNBC cells are highly heterogeneous populations [36], and different subpopulations of cells have their own characteristics, some may be more differentiated, but others exhibit CSC-like characteristics [37], which together contribute to the plasticity of tumor cells. Enhanced tumor cell plasticity has been shown to be an important driving force for tumor progression toward malignancy and recurrence of drug resistance [38][39][40].…”

Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression

“…Recent articles have reviewed the importance of CSCs in TNBC progression and therapeutic resistance [ 18 , 19 , 20 , 21 , 22 , 23 ]. TNBCs are enriched with CD44+/CD24−/ALDH1+ CSCs that contribute to metastases, chemoresistance and poor clinical outcomes [ 24 , 25 , 26 , 27 , 28 ].…”

“…Resistance of TNBC CSCs to DNA damage is mediated by phenotypic heterogeneity and epithelial–mesenchymal plasticity, which are driven in part by the ZEB1 transcription factor (TF) [ 29 , 30 , 31 , 32 ]. The WNT, NF-κB and NOTCH pathways are activated in TNBC CSCs [ 20 , 33 ]. Activation of Sonic Hedgehog (SHH) has also been identified as a pathway that contributes to the TNBC CSC state [ 33 , 34 , 35 ].…”

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study

“…Leptin plays a role on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu (Amitabha et al, 2017). Leptin has been connected to breast cancer initiation, development, and progression through signaling transduction network (Ehmsen et al, 2020). Elevated blood leptin concentrations or increased leptin receptors expression are associated with poor prognosis, lymph node involvement and cancer metastasis (Tsung-Chieh et al, 2021).…”