Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia

Jw, Cui; Lm, Vecchiarelli-Federico; Yj, Li; Gj, Wang; Ben‐David, Yaacov

doi:10.1038/leu.2009.20

Cited by 33 publications

(49 citation statements)

References 30 publications

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“…by guest www.bloodjournal.org From erythropoiesis is quite similar to its role evidenced in erythroleukemic cells. 47,48 Moreover, Spi-1/Pu.1 has also been reported to play a similar role in erythroleukemic cells as well as during fetal erythropoiesis, 49,50 although its role during normal adult erythropoiesis has not been clearly addressed. An interesting perspective raised by all these data will be to know if this common property of Fli-1 and Spi-1/Pu.1 relies on the deregulation of common targets genes such as genes involved in ribosome biogenesis that we recently identified in erythroleukemic cells.…”

Section: Discussionmentioning

confidence: 99%

Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation

Starck

Weiss‐Gayet

Gonnet

et al. 2010

Blood

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This study investigated the role of the ETS transcription factor Fli-1 in adult myelopoiesis using new transgenic mice allowing inducible Fli-1 gene deletion. Fli-1 deletion in adult induced mild thrombocytopenia associated with a drastic decrease in large mature megakaryocytes number. Bone marrow bipotent megakaryocyticerythrocytic progenitors (MEPs) increased by 50% without increase in erythrocytic and megakaryocytic common myeloid progenitor progeny, suggesting increased production from upstream stem cells. These MEPs were almost unable to generate pure colonies containing large mature megakaryocytes, but generated the same total number of colonies mainly identifiable as erythroid colonies containing a reduced number of more differentiated cells. Cytological and fluorescenceactivated cell sorting analyses of MEP progeny in semisolid and liquid cultures confirmed the drastic decrease in large mature megakaryocytes but revealed a surprisingly modest (50%) reduction of CD41-positive cells indicating the persistence of a megakaryocytic commitment potential. Symmetrical increase and decrease of monocytic and granulocytic progenitors were also observed in the progeny of purified granulocytic-monocytic progenitors and common myeloid progenitors. In summary, this study indicates that Fli-1 controls several lineages commitment decisions at the stem cell, MEP, and granulocytic-monocytic progenitor levels, stimulates the proliferation of committed erythrocytic progenitors at the expense of their differentiation, and is a major regulator of late stages of megakaryocytic differentiation. (Blood. 2010;116(23):4795-4805) IntroductionMature blood cells in adults are permanently regenerated from a limited pool of pluripotent hematopoietic stem cells (HSCs) localized in the bone marrow. This process occurs through the hierarchical generation of intermediate progenitors with more and more restricted differentiation and proliferation potential that can be prospectively purified. According to current models, myeloid lineages are derived from a common myeloid progenitor (CMP) generating 2 distinct bipotent progenitors, the megakaryocyticerythrocytic progenitors (MEPs) and the granulocytic-monocytic progenitors (GMP). 1 MEPs generate in turn erythrocytic and megakaryocytic monopotent progenitors, whereas GMP generate granulocytic and monocytic monopotent progenitors. Increasing data also indicate an alternative pathway generating MEPs directly from HSCs. [2][3][4] All this process is controlled by permanent crosstalk between extracellular signals and intracellular regulatory networks of transcription factors. Although having no instructive role, erythropoietin (EPO) is the major cytokine controlling erythropoiesis through the stimulation of proliferation and survival of committed erythrocytic progenitors expressing the specific receptor EPOR. 5 Thrombopoietin (TPO) is the major cytokine controlling megakaryopoiesis through the stimulation of proliferation and differentiation of committed megakaryocytic progenitors expressing the sp...

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Section: Discussionmentioning

confidence: 99%

Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation

Starck

Weiss‐Gayet

Gonnet

et al. 2010

Blood

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“…These results suggest that Fli-1 overexpression in erythroblasts alters their responsiveness to Epo and triggers abnormal proliferation by switching the signaling event(s) associated with terminal differentiation to proliferation (Zochodne et al, 2000). The constitutive suppression of Fli-1, mediated through RNA interference or dominant negative protein expression has revealed an essential role for continuous Fli-1 overexpression in the maintenance and survival of the malignant phenotype in both murine and human erythroleukemia (Cui et al, 2009). …”

Section: Functionmentioning

confidence: 98%

“…Similar to other Ets proteins, Fli-1 is a nuclear transcription factor and is generally localized within the nucleus, although Fli-1 protein has also been detected in the cytoplasm of specific cell types (Cui et al, 2009;Pusztaszeri et al, 2006).…”

Section: Localisationmentioning

confidence: 99%

“…A comparison of the Fli-1 3' Ets domain to other structures has suggested that this 3' Ets domain uses a new variation of the winged helix-turn-helix motif for binding to DNA (Liang et al, 1994b). Fli-1 binds to DNA in a sequence-specific manner, and it has been determined that the optimal DNA binding sequence for Fli-1 is ACCGGAAG/aT/c (Solomon and Kaldis, 1998;Mao et al, 1994;Cui et al, 2009). The bases flanking the core GGA Ets DNA-binding motif synergistically contribute to binding specificity among different Ets transcription factors.…”

Section: Descriptionmentioning

confidence: 99%

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FLI1 (Friend leukemia virus integration 1)

Lm¹,

Haeri²,

Ben‐David³

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…FLI‐1 is preferentially expressed in the hematopoietic and vascular endothelial cells and plays an important role in normal cell function and malignant transformation 6, 7. It has been widely accepted as an oncogene contributing to various malignancies, such as malignant hematological diseases and some solid tumors, including breast cancer 8, 9, 10, 11, 12, 13, 14. In our previous study, we showed that the expression of FLI‐1 upregulated in breast cancer tissues compared with that in the nontumor adjacent tissues.…”

Section: Introductionmentioning

confidence: 99%

Friend leukemia virus integration 1 is a predictor of poor prognosis of breast cancer and promotes metastasis and cancer stem cell properties of breast cancer cells

et al. 2018

Cancer Medicine

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Breast cancer is the most common cancer in women worldwide; despite the developments in diagnosis and therapy, recurrence and metastasis remain the main causes of death among patients with breast cancer. This study aimed to identify a promising biomarker for this disease. The study clarified (1) the association between Friend leukemia virus integration 1 (FLI‐1) and various molecular subtypes and (2) the prognostic value of FLI‐1 in breast cancer. To the best of our knowledge, this study is the first to report that FLI‐1 is a predictor of poor prognosis in patients with breast cancer and overexpressed in the triple negative breast cancer (TNBC) subtype. To further verify the effect of FLI‐1 in promoting the metastasis of TNBC, we performed a series of functional experiments in vitro and orthotopic xenograft experiments in the mammary fat pad of nude mice. FLI‐1, as a transcription factor, bound to the promoters of key EMT‐related genes (CDH1 and VIM), and regulated their expressions at the transcriptional level, thus induced epithelial‐mesenchymal transition (EMT). The overexpression of FLI‐1 significantly upregulated the expression of mesenchymal markers. After the modulation of FLI‐1, the changes in mammary stem cell markers (ALDH1A1 and CD133) and the capacity to form mammospheres were consistent with those of the EMT‐related markers. The orthotopic xenograft models further confirmed that the attenuation of stem cell traits after silencing FLI‐1 decreased the ability of tumorigenesis. These results indicate that FLI‐1 is a useful predictor of poor prognosis in patients with breast cancer. Furthermore, the preliminary exploration of metastatic mechanism in the patients with TNBC will provide a potential target to treat breast cancer in the near future.

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Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia

Cited by 33 publications

References 30 publications

Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation

Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation

FLI1 (Friend leukemia virus integration 1)

Friend leukemia virus integration 1 is a predictor of poor prognosis of breast cancer and promotes metastasis and cancer stem cell properties of breast cancer cells

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