Notch and breast cancer metastasis: Current knowledge, new sights and targeted therapy (Review)

Abstract

Breast cancer is the most common type of invasive cancer in females and metastasis is one of the major causes of breast cancer-associated mortality. Following detachment from the primary site, disseminated tumor cells (DTCs) enter the bloodstream and establish secondary colonies during the metastatic process. An increasing amount of studies have elucidated the importance of Notch signaling in breast cancer metastasis; therefore, the present review focuses on the mechanisms by which Notch contributes to the occurrence of breast cancer DTCs, increases their motility, establishes interactions with the tumor microenvironment, protects DTCs from host surveillance and finally facilitates secondary colonization. Identification of the underlying mechanisms of Notch-associated breast cancer metastasis will provide additional insights that may contribute towards the development of novel Notch-targeted therapeutic strategies, which may aid in reducing metastasis, culminating in an improved patient prognosis. Contents 1. Introduction 2. Notch signaling 3. Notch and biased cell fate determinants 4. Notch and local invasion 5. Notch and survival in circulation 6. Notch and secondary colonization 7. Notch-associated microRNAs in breast cancer metastasis 8. Application of Notch signaling in the clinical treatment of breast cancer 9. Conclusion

Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy

“…Pin1 also promotes EMT through upregulation of STAT3 and NF-κB in human gallbladder cancer [ 172 ]. Additionally, NOTCH signaling drives metastasis in numerous cancers [ 173 , 174 , 175 , 176 ] and Pin1 prevents NOTCH1 and NOTCH4 from undergoing FBXW7-mediated degradation, leading to an increase in breast cancer stem cells’ (CSCs) self-renewal and metastasis [ 177 ]. In addition to protein stability, Pin1 also activates NOTCH1 transcriptional activity by facilitating γ-secretase-mediated cleavage and release of the active intracellular domain.…”

Targeting Signaling Pathway Networks in Several Malignant Tumors: Progresses and Challenges

“…The American Cancer Association states that BC can be classified into four BC molecular subtypes with prognostic differences in terms of patient outcome on the basis of the presence or absence of the expression of specific biological markers: ERs, progesterone receptors, and HER2. The Notch system, in cooperation with the VEGF pathway, engages in the adjusting of angiogenesis and sprouting in BC (Zhang et al, 2019). Notch expression is controlled by hypoxia and inflammatory cytokines (IL-1, IL-6, and leptin).…”

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

“…As a potential factor in cell fate, increasing evidence has shown that Notch signaling plays like a double-edged sword in cancer, and it has both oncogene and onco-suppressor activities [ 248 , 249 , 250 , 251 , 252 , 253 , 254 ]. It has been reported that metastasis of GC cells is tightly regulated by Notch/PTEN/Akt axis.…”