Breast Cancer Stem Cells: Biomarkers, Identification and Isolation Methods, Regulating Mechanisms, Cellular Origin, and Beyond

Zhang, Xiaoli; Powell, Kimerly; Li, Lang

doi:10.3390/cancers12123765

Cited by 72 publications

(63 citation statements)

References 245 publications

(384 reference statements)

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“…Breast cancer stem cells (BCSCs) are heterogeneous subpopulations of breast cancer cells that have properties of differentiation and self-renewal [4]. Additionally, these BCSC subpopulations are known to influence therapeutic response and clinical outcomes [5]. Owing to these characteristics, the development of treatments targeting BCSCs is an emerging research hotspot.…”

Section: Introductionmentioning

confidence: 99%

Physalin A, 13,14-Seco-16, 24-Cyclo-Steroid, Inhibits Stemness of Breast Cancer Cells by Regulation of Hedgehog Signaling Pathway and Yes-Associated Protein 1 (YAP1)

Choi

Liu

et al. 2021

IJMS

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The Hedgehog (HH) signaling pathway plays an important role in embryonic development and adult organ homeostasis. Aberrant activity of the Hedgehog signaling pathway induces many developmental disorders and cancers. Recent studies have investigated the relationship of this pathway with various cancers. GPCR-like protein Smoothened (SMO) and the glioma-associated oncogene (GLI1) are the main effectors of Hedgehog signaling. Physalin A, a bioactive substance derived from Physalis alkekengi, inhibits proliferation and migration of breast cancer cells and mammospheres formation. Physalin A-induced apoptosis and growth inhibition of mammospheres, and reduced transcripts of cancer stem cell (CSC) marker genes. Physalin A reduced protein expressions of SMO and GLI1/2. Down-regulation of SMO and GLI1 using siRNA inhibited mammosphere formation. Physalin A reduced mammosphere formation by reducing GLI1 gene expression. Down-regulation of GLI1 reduced CSC marker genes. Physalin A reduced protein level of YAP1. Down-regulation of YAP1 using siRNA inhibited mammosphere formation. Physalin A reduced mammosphere formation through reduction of YAP1 gene expression. Down-regulation of YAP1 reduced CSC marker genes. We showed that treatment of MDA-MB-231 breast cancer cells with GLI1 siRNA induced inhibition of mammosphere formation and down-regulation of YAP1, a Hippo pathway effector. These results show that Hippo signaling is regulated by the Hedgehog signaling pathway. Physalin A also inhibits the canonical Hedgehog and Hippo signaling pathways, CSC-specific genes, and the formation of mammospheres. These findings suggest that physalin A is a potential therapeutic agent for targeting CSCs.

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Section: Introductionmentioning

confidence: 99%

Physalin A, 13,14-Seco-16, 24-Cyclo-Steroid, Inhibits Stemness of Breast Cancer Cells by Regulation of Hedgehog Signaling Pathway and Yes-Associated Protein 1 (YAP1)

Choi

Liu

et al. 2021

IJMS

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“…In fact, there are studies describing BCSCs as key elements in therapy resistance, breast cancer relapse, and metastasis [2,5,15,25,[30][31][32]. Accordingly, a high proportion of BCSCs within breast tumours have been demonstrated as being correlated with a poor outcome [33]. Therefore, BCSCs constitute an area of major concern in oncology, highlighting the need for the development of new therapeutic strategies that allow the overcome of therapy resistance for the benefit of breast cancer patients.…”

Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

Breast Cancer Stem Cell Membrane Biomarkers: Therapy Targeting and Clinical Implications

Conde

Ribeiro

Paredes

2022

Cells

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Breast cancer is the most common malignancy affecting women worldwide. Importantly, there have been significant improvements in prevention, early diagnosis, and treatment options, which resulted in a significant decrease in breast cancer mortality rates. Nevertheless, the high rates of incidence combined with therapy resistance result in cancer relapse and metastasis, which still contributes to unacceptably high mortality of breast cancer patients. In this context, a small subpopulation of highly tumourigenic cancer cells within the tumour bulk, commonly designated as breast cancer stem cells (BCSCs), have been suggested as key elements in therapy resistance, which are responsible for breast cancer relapses and distant metastasis. Thus, improvements in BCSC-targeting therapies are crucial to tackling the metastatic progression and might allow therapy resistance to be overcome. However, the design of effective and specific BCSC-targeting therapies has been challenging since there is a lack of specific biomarkers for BCSCs, and the most common clinical approaches are designed for commonly altered BCSCs signalling pathways. Therefore, the search for a new class of BCSC biomarkers, such as the expression of membrane proteins with cancer stem cell potential, is an area of clinical relevance, once membrane proteins are accessible on the cell surface and easily recognized by specific antibodies. Here, we discuss the significance of BCSC membrane biomarkers as potential prognostic and therapeutic targets, reviewing the CSC-targeting therapies under clinical trials for breast cancer.

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“…Despite experimental evidence indicate that CSCs may contribute to breast tumor progression and metastatic spread [146,147], the real nature of CSCs in breast malignancy remains to be elucidated [148]. Indeed, the existence of CSCs has been subjected to controversy, but the CSC model is attractive toward novel antitumor strategies [149,150].…”

Section: Role Of Fak In Csc Self-renewal and Maintenancementioning

confidence: 99%

Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression

Rigiracciolo

Cirillo

Talia

et al. 2021

Cancers

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Breast cancer represents the most common diagnosed malignancy and the main leading cause of tumor-related death among women worldwide. Therefore, several efforts have been made in order to identify valuable molecular biomarkers for the prognosis and prediction of therapeutic responses in breast tumor patients. In this context, emerging discoveries have indicated that focal adhesion kinase (FAK), a non-receptor tyrosine kinase, might represent a promising target involved in breast tumorigenesis. Of note, high FAK expression and activity have been tightly correlated with a poor clinical outcome and metastatic features in several tumors, including breast cancer. Recently, a role for the integrin-FAK signaling in mechanotransduction has been suggested and the function of FAK within the breast tumor microenvironment has been ascertained toward tumor angiogenesis and vascular permeability. FAK has been also involved in cancer stem cells (CSCs)-mediated initiation, maintenance and therapeutic responses of breast tumors. In addition, the potential of FAK to elicit breast tumor-promoting effects has been even associated with the capability to modulate immune responses. On the basis of these findings, several agents targeting FAK have been exploited in diverse preclinical tumor models. Here, we recapitulate the multifaceted action exerted by FAK and its prognostic significance in breast cancer. Moreover, we highlight the recent clinical evidence regarding the usefulness of FAK inhibitors in the treatment of breast tumors.

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Breast Cancer Stem Cells: Biomarkers, Identification and Isolation Methods, Regulating Mechanisms, Cellular Origin, and Beyond

Cited by 72 publications

References 245 publications

Physalin A, 13,14-Seco-16, 24-Cyclo-Steroid, Inhibits Stemness of Breast Cancer Cells by Regulation of Hedgehog Signaling Pathway and Yes-Associated Protein 1 (YAP1)

Physalin A, 13,14-Seco-16, 24-Cyclo-Steroid, Inhibits Stemness of Breast Cancer Cells by Regulation of Hedgehog Signaling Pathway and Yes-Associated Protein 1 (YAP1)

Breast Cancer Stem Cell Membrane Biomarkers: Therapy Targeting and Clinical Implications

Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression

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