Mammary stem cells, self-renewal pathways, and carcinogenesis

Liu, Suling; Dontu, Gabriela; Wicha, Max S.

doi:10.1186/bcr1021

Cited by 400 publications

(344 citation statements)

References 67 publications

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“…Thus, deregulation of EMT-regulating factors in the mammary gland could induce EMT in epithelial mammary cells and/or in stem-like cells, and thus, these cells could later acquire mesenchymal characteristics with invasive and self-renewal capabilities, enabling these cells to develop micrometastasis and macrometastasis in distant organs. These data also support the hypothesis that breast cancer cells may have a stem cell origin (49)(50)(51).…”

Section: Discussionsupporting

confidence: 77%

Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis

Ben-Batalla¹,

Seoane²,

García‐Caballero³

et al. 2010

J. Clin. Invest.

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The Pit-1 transcription factor (also know as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. Some of these protumorigenic effects of Pit-1 were mediated by upregulation of Snai1, an inductor of the epithelial-mesenchymal transition. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumor, high expression of Pit-1 was significantly correlated with Snai1 positivity. Notably, in these patients elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node-positive breast cancer and may represent a new therapeutic target.

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Section: Discussionsupporting

confidence: 77%

Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis

Ben-Batalla¹,

Seoane²,

García‐Caballero³

et al. 2010

J. Clin. Invest.

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“…Other studies have shown that lower levels of p53 results in increased mammary stem/progenitors (Tao et al, 2011) and lack of pRb has been shown to promote expansion of multi-potent stem cells (Gutierrez et al, 2008). In addition, the ST antigen has been shown to activate Notch, Hedgehog and Wnt pathways (Ali-Seyed et al, 2006) all of which are associated with stem cell self-renewal as well as breast carcinogenesis (Liu et al, 2005). Furthermore, overexpression of telomerase is also known to enhance proliferation of adult stem cells (Sarin et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Yet, the perturbations required for the tumorigenic transformation of these primitive cells remains unknown. Given the striking parallels between normal stem cells and cancer cells, including extensive self-renewal, expression of telomerase and ability to grow in anchorage-independent conditions (Liu et al, 2005), it is possible that these immature cells require fewer alterations for transformation compared with their more differentiated counterparts that lack these properties.…”

Section: Introductionmentioning

confidence: 99%

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

et al. 2011

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“…Approximately 50% of human breast cancers show defects in Notch signaling, largely mediated by reduced expression of the Notch inhibitor, NUMB [41][42][43][44][45]. Evidence support that Notch plays a key role, in the regulation of asymmetric cell fate decisions in human mammary stem cells [41][42][43][44][45]. Notch activation requires the action of the proteolytic enzyme gamma secretase.…”

Section: Targeting Tics In Human Breast Cancersmentioning

confidence: 99%

Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer

Creighton

Chang‐Claude

Rosen

2010

J Mammary Gland Biol Neoplasia

232

192

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There is increasing support for the hypothesis that most tumors contain a subpopulation of cells, referred to here as tumor initiating cells (TICs), with the ability to self-renew and to regenerate all the cell types within the tumor. TICs are enriched in breast cancer patients after common treatments, indicating their intrinsic therapeutic resistance. Two independently-derived gene transcription "signatures" of TICs from different studies indicate enrichment of TICs within the recently-identified "claudin-low" intrinsic molecular subtype of breast cancer. These are characterized by high expression of markers associated with epithelial-mesenchymal transition (EMT), suggesting that claudin-low cells may arise from more immature stem or progenitor cells than other breast cancers. EMT is a process by which cells acquire molecular alterations that facilitate dysfunctional cell-cell adhesive interactions and junctions, as well as a more spindle-shaped morphology. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Induction of EMT in immortalized human mammary epithelial cells results in an increased ability to form mammospheres, and in the expression of stem cell and TIC markers, suggesting that there may be a direct link between the EMT and the gain of TIC properties. Targeting specific molecular pathways-such as Notch, Wnt, and TGFß-associated with development and EMT in the TIC subpopulation, in addition to conventional chemo-and radiation therapies that target the bulk tumor, may ultimately provide a more effective strategy in treating breast cancer. Here, we review recent evidence of the involvement of EMT in breast cancer TICs, focusing on clinical studies.

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Mammary stem cells, self-renewal pathways, and carcinogenesis

Cited by 400 publications

References 67 publications

Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis

Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer

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