TGFβ/cyclin D1/Smad-mediated inhibition of BMP4 promotes breast cancer stem cell self-renewal activity

Yan, Gang; Dai, Meiou; Zhang, Chenjing; Poulet, Sophie; Moamer, Alaa; Wang, Ni; Boudreault, Julien; Ali, Suhad; Lebrun, Jean-Jacques

doi:10.1038/s41389-021-00310-5

Cited by 18 publications

(15 citation statements)

References 75 publications

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“…However, in triple-negative breast cancer (TNBC) cells, TGF-β inhibits the expression of BMP-4 through the Smad pathway and cyclin D1. Thus, TGF-β enhances tumor formation and increases the highly tumorigenic CD44 high CD24 low CSC population ( Yan et al, 2021 ). Whissel et al found that BMP4 transcription is regulated by GATA-binding protein 6 (GATA6), which is related to the self-renewal of adenoma stem cells in the colon ( Whissell et al, 2014 ).…”

Section: Effect Of Bone Morphogenetic Proteins On Cancer Stem Cellsmentioning

confidence: 99%

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

Ehata

Miyazono

2022

Front. Cell Dev. Biol.

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Bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, are multifunctional cytokines. BMPs have a broad range of functions, and abnormalities in BMP signaling pathways are involved in cancer progression. BMPs activate the proliferation of certain cancer cells. Malignant phenotypes of cancer cells, such as increased motility, invasiveness, and stemness, are enhanced by BMPs. Simultaneously, BMPs act on various cellular components and regulate angiogenesis in the tumor microenvironment. Thus, BMPs function as pro-tumorigenic factors in various types of cancer. However, similar to TGF-β, which shows both positive and negative effects on tumorigenesis, BMPs also act as tumor suppressors in other types of cancers. In this article, we review important findings published in the recent decade and summarize the pro-oncogenic functions of BMPs and their underlying mechanisms. The current status of BMP-targeted therapies for cancers is also discussed.

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Section: Effect Of Bone Morphogenetic Proteins On Cancer Stem Cellsmentioning

confidence: 99%

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

Ehata

Miyazono

2022

Front. Cell Dev. Biol.

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“…A possible explanation for the favorable prognosis in our cohort could be the association of cyclin D1 with lowgrade tumors and ER positive tumors, which are known to have a lower breast cancer stem cell population and hence tend to have a better prognosis. 41 Since many studies have succeeded in finding a prognostic value for cyclin D1 overexpression in luminal (hormone receptor positive) BC, 12,21,27,28,42 we sought to further explore the prognostic impact of cyclin D1 on hormone receptor-positive tumors. Upon analysis of prognosis in luminal tumors, which accounted for 71.1% (713/1003) of our cohort, no prognostic correlation was observed in this subset of BC, which is inconsistent with previous studies, where favorable prognosis was seen in this subset of BC.…”

Section: Discussionmentioning

confidence: 99%

High Expression of Cyclin D1 is an Independent Marker for Favorable Prognosis in Middle Eastern Breast Cancer

Siraj¹,

Parvathareddy²,

Annaiyappanaidu³

et al. 2021

OTT

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The cyclin D1 protein regulates cell cycle progression which is mediated by its interactions with cyclin-dependent kinases. Over-expression of cyclin D1 has been observed in several human cancers. This study was conducted to evaluate cyclin D1 expression in a large cohort of Middle Eastern breast cancers and determine its prognostic significance. Patients and Methods: Cyclin D1 expression was assessed immunohistochemically and its association with clinico-pathological parameters was analyzed in 1003 breast cancer patients. Results: Cyclin D1 was over-expressed in 59.4% (596/1003) of cases and significantly associated with a subset of breast cancers having favorable prognostic features, such as low grade (p < 0.0001), low stage (p = 0.0276), estrogen receptor (p < 0.0001) and progesterone receptor positive (p < 0.0001) tumors. An inverse association was found with triple negative breast cancers (p < 0.0001). More importantly, cyclin D1 expression was an independent predictor of favorable overall survival in our cohort (hazard ratio = 0.70; 95% confidence interval = 0.50-0.98; p = 0.0395). Also, tumors that highly expressed cyclin D1 had a longer recurrence-free survival. However, this significant association was seen only in univariate analysis. We also found cyclin D1 to be associated with phospho-Rb in luminal subtype of breast cancer and co-expression of both these markers was an independent predictor of luminal A breast cancer. Conclusion:Our results reinforced the role of cyclin D1 in breast cancer pathology and revealed its expression as a valuable independent prognostic indicator for breast cancer from Middle Eastern ethnicity.

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“…It also serves to enrich the population of cancer stem cells and induce angiogenesis. Cyclin D1 is a vital modulator of mammary and embryonic stem cells and is known to assist transforming growth factor β (TGF-β) in inducing stem cell renewal in triple-negative breast cancer cells [55,56]. Therefore, many promising studies have focussed on downregulating cyclin D1 for enhanced anticancer action [57][58][59][60].…”

Section: Activated Ampk Downregulates Cyclin Proteins and Induces Cel...mentioning

confidence: 99%

Targeting Breast Cancer and Their Stem Cell Population through AMPK Activation: Novel Insights

Uprety

Abrahamse

2022

Cells

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Despite some significant advancements, breast cancer has become the most prevalent cancer in the world. One of the main reasons for failure in treatment and metastasis has been attributed to the presence of cancer initiating cells—cancer stem cells. Consequently, research is now being focussed on targeting cancer cells along with their stem cell population. Non-oncology drugs are gaining increasing attention for their potent anticancer activities. Metformin, a drug commonly used to treat type 2 diabetes, is the best example in this regard. It exerts its therapeutic action by activating 5′ adenosine monophosphate-activated protein kinase (AMPK). Activated AMPK subsequently phosphorylates and targets several cellular pathways involved in cell growth and proliferation and the maintenance of stem-like properties of cancer stem cells. Therefore, AMPK is emerging as a target of choice for developing effective anticancer drugs. Vanadium compounds are well-known PTP inhibitors and AMPK activators. They find extensive applications in treatment of diabetes and obesity via PTP1B inhibition and AMPK-mediated inhibition of adipogenesis. However, their role in targeting cancer stem cells has not been explored yet. This review is an attempt to establish the applications of insulin mimetic vanadium compounds for the treatment of breast cancer by AMPK activation and PTP1B inhibition pathways.

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TGFβ/cyclin D1/Smad-mediated inhibition of BMP4 promotes breast cancer stem cell self-renewal activity

Cited by 18 publications

References 75 publications

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

High Expression of Cyclin D1 is an Independent Marker for Favorable Prognosis in Middle Eastern Breast Cancer

Targeting Breast Cancer and Their Stem Cell Population through AMPK Activation: Novel Insights

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