Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis

Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. The β-lapachone (bL) compound is widely used to treat cancer development; however, its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast-cancer stem-cell (BCSC) marker-positive cells, MDA-MB-231. MDA-MB-231 cells, which are negative for reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H):quinone oxidoreductase (NQO1) expression, were constructed to stably express NQO1 (NQO1 stable cells). The effect of bL on these cells was evaluated by wound healing and Transwell cell-culture chambers, ALDEFLUOR assay, and mammosphere formation assay. Here, we show that bL inhibited the proliferative ability of mammospheres derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. The bL treatment efficiently downregulated the expression level of BCSC markers cluster of differentiation 44 (CD44), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), and discs large (DLG)-associated protein 5 (DLGAP5) that was recently identified as a stem-cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulated cell proliferation and migration activities. These results strongly suggest that bL could be a therapeutic agent for targeting breast-cancer stem-cells with proper NQO1 expression.

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Targeting CXCR1 on breast cancer stem cells: signaling pathways and clinical application modelling

Oncotarget ◽

10.18632/oncotarget.6234 ◽

2015 ◽

Vol 6 (41) ◽

pp. 43375-43394 ◽

Cited By ~ 36

Author(s):

Laura Brandolini ◽

Loredana Cristiano ◽

Alessia Fidoamore ◽

Maria De Pizzol ◽

Erica Di Giacomo ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Signaling Pathways ◽

Clinical Application ◽

Breast Cancer Stem Cells

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Heterogenous Effect of Risk Factors on Breast Cancer across the Breast Density Categories in a Korean Screening Population

Cancers ◽

10.3390/cancers12061391 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1391

Author(s):

Boyoung Park ◽

Se-Eun Lim ◽

HyoJin Ahn ◽

Junghyun Yoon ◽

Yun Su Choi

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Postmenopausal Women ◽

Breast Density ◽

Breast Imaging ◽

Hormone Replacement ◽

Cancer Development ◽

Age At Menarche ◽

Breast Cancer Development ◽

Heterogeneous Association

We evaluated the heterogeneity of the effect of known risk factors on breast cancer development based on breast density by using the Breast Imaging-Reporting and Data System (BI-RADS). In total, 4,898,880 women, aged 40–74 years, who participated in the national breast cancer screening program in 2009–2010 were followed up to December 2018. Increased age showed a heterogeneous association with breast cancer (1-year hazard ratio (HR) = 0.92, 1.00 (reference), 1.03, and 1.03 in women with BI-RADS density category 1, 2, 3, and 4, respectively; P-heterogeneity < 0.001). More advanced age at menopause increased breast cancer risk in all BI-RADS categories. This was more prominent in women with BI-RADS density category 1 but less prominent in women in other BI-RADS categories (P-heterogeneity = 0.009). In postmenopausal women, a family history of breast cancer, body mass index ≥ 25 kg/m2, and smoking showed a heterogeneous association with breast cancer across all BI-RADS categories. Other risk factors including age at menarche, menopause, hormone replacement therapy after menopause, oral contraceptive use, and alcohol consumption did not show a heterogeneous association with breast cancer across the BI-RADS categories. Several known risk factors of breast cancer had a heterogeneous effect on breast cancer development across breast density categories, especially in postmenopausal women.

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Depression and the lower risk for breast cancer development in middle-aged women: a prospective study

Psychological Medicine ◽

10.1017/s0033291703007499 ◽

2003 ◽

Vol 33 (6) ◽

pp. 1111-1117 ◽

Cited By ~ 15

Author(s):

I. NYKLÍČEK ◽

W. J. LOUWMAN ◽

P. W. M. VAN NIEROP ◽

C. J. WIJNANDS ◽

J.-W. W. COEBERGH ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Depressive Symptoms ◽

Lower Risk ◽

Protective Factor ◽

Depression Scale ◽

Population Based ◽

Cancer Development ◽

Breast Cancer Development ◽

Increased Risk

Background. Depression has been hypothesized to be potentially linked to an increased risk of breast cancer. Few studies have addressed this question using population-based cohorts and prospective designs, adjusting for known biomedical risk factors. This has been done in the present investigation.Method. Participants were 5191 women from a cohort of women born between 1941 and 1947 and living in the city of Eindhoven, The Netherlands. All women completed questionnaires regarding the presence of depressive symptoms (Edinburgh Depression Scale) and background (demographic, medical and lifestyle) variables. The questionnaire data were linked with the records of the Eindhoven Cancer Registry. These records provided data on breast cancer diagnoses, which took place up to 5 years after the questionnaire screening.Results. Fifty-eight women (1·1%) were found to have developed breast cancer at least 2 years after the questionnaire screening. After controlling for 15 potential risk factors, of which family history of breast cancer, hypothyroidism and unilateral oophorectomy were significant predictors of breast cancer development, women with depressive symptoms had a lower risk of subsequent breast cancer (OR=0·29, 95% CI=0·09–0·92, P=0·04).Conclusions. Depressive complaints may be associated with a protective factor involved in the development of breast cancer. Some of the possible candidates for this factor are discussed.

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42P Expression of WNT, Hedgehog and NOTCH signaling pathways in HER-2 overexpressed and triple negative subtypes of breast cancer with high and low content of cancer stem cells

Annals of Oncology ◽

10.1016/j.annonc.2020.03.176 ◽

2020 ◽

Vol 31 ◽

pp. S30

Author(s):

S. Demidov ◽

S. Sazonov ◽

A. Brilliant ◽

Y. Brilliant

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Notch Signaling ◽

Signaling Pathways ◽

Triple Negative ◽

Her 2

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Breast cancer growth and metastasis: interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition

Breast Cancer Research ◽

10.1186/bcr2876 ◽

2011 ◽

Vol 13 (3) ◽

Cited By ~ 117

Author(s):

Naoko Takebe ◽

Ronald Q Warren ◽

S Percy Ivy

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Signaling Pathways ◽

Epithelial To Mesenchymal Transition ◽

Cancer Growth ◽

Mesenchymal Transition ◽

Breast Cancer Growth ◽

Embryonic Signaling

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HDL and LDL: Potential New Players in Breast Cancer Development

Journal of Clinical Medicine ◽

10.3390/jcm8060853 ◽

2019 ◽

Vol 8 (6) ◽

pp. 853 ◽

Cited By ~ 21

Author(s):

Lídia Cedó ◽

Srinivasa T. Reddy ◽

Eugènia Mato ◽

Francisco Blanco-Vaca ◽

Joan Carles Escolà-Gil

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Oxidative Modification ◽

Cancer Development ◽

High Density Lipoproteins ◽

Breast Cancer Development

Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer.

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