FOXO factors and breast cancer: outfoxing endocrine resistance

Bullock, Martyn

doi:10.1530/erc-15-0461

Cited by 41 publications

(38 citation statements)

References 154 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In mammalian species, there are four members of the FoxO family: FoxO1 (FKHR), FoxO3 (FKHRL1), FoxO4 (AFX), and FoxO6 [11]. FoxO1 and FoxO3 proteins are greater than 650 amino acids in size, which are larger than FoxO4 and FoxO6 (nearly 500 amino acids).…”

Section: The Foxo Familymentioning

confidence: 99%

“…FoxO1 and FoxO3 proteins are greater than 650 amino acids in size, which are larger than FoxO4 and FoxO6 (nearly 500 amino acids). Although, the FoxO6 gene exhibits major structural differences as compared to the other three family gene members [11]. The four FoxO protein members share obvious sequence homology and possess four clearly different functional motifs, which include a forkhead domain, nuclear localization, nuclear export, and transactivation domains ( Figure 1) [12,13].…”

Section: The Foxo Familymentioning

confidence: 99%

See 1 more Smart Citation

The Roles of FoxO Transcription Factors in Regulation of Bone Cells Function

Chen

et al. 2020

IJMS

View full text Add to dashboard Cite

Forkhead box class O family member proteins (FoxOs) are evolutionarily conserved transcription factors for their highly conserved DNA-binding domain. In mammalian species, all the four FoxO members, FoxO1, FoxO3, FoxO4, and FoxO6, are expressed in different organs. In bone, the first three members are extensively expressed and more studied. Bone development, remodeling, and homeostasis are all regulated by multiple cell lineages, including osteoprogenitor cells, chondrocytes, osteoblasts, osteocytes, osteoclast progenitors, osteoclasts, and the intercellular signaling among these bone cells. The disordered FoxOs function in these bone cells contribute to osteoarthritis, osteoporosis, or other bone diseases. Here, we review the current literature of FoxOs for their roles in bone cells, focusing on helping researchers to develop new therapeutic approaches and prevent or treat the related bone diseases.

show abstract

Section: The Foxo Familymentioning

confidence: 99%

Section: The Foxo Familymentioning

confidence: 99%

The Roles of FoxO Transcription Factors in Regulation of Bone Cells Function

Chen

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…26,27) are negatively regulated by the PI3K/AKT signaling (28). FoxO3a has been recognized as a tumor suppressor gene in breast cancer (29) and restoration of its expression and activity is being exploited in cancer therapy (26,30). The results reported here confirm our hypothesis, as lamotrigine treatment markedly reduces the phosphorylation of AKT and its direct downstream targets FoxO3a and GSK-3b, while, in agreement with another study conducted on human neuroblastoma SH-SY5Y cell line (31), it did not have any effect on ERK/ MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

FoxO3a Mediates the Inhibitory Effects of the Antiepileptic Drug Lamotrigine on Breast Cancer Growth

Pellegrino

Rizza

Nigro

et al. 2018

Molecular Cancer Research

View full text Add to dashboard Cite

Breast cancer is a complex and heterogeneous disease, with distinct histologic features dictating the therapy. Although the clinical outcome of breast cancer patients has been considerably improved, the occurrence of resistance to common endocrine and chemotherapy treatments remains the major cause of relapse and mortality. Thus, efforts in identifying new molecules to be employed in breast cancer therapy are needed. As a "faster" alternative to reach this aim, we evaluated whether lamotrigine, a broadly used anticonvulsant, could be "repurposed" as an antitumoral drug in breast cancer. Our data show that lamotrigine inhibits the proliferation, the anchorage-dependent, and independent cell growth in breast cancer cells (BCC), including hormone-resistant cell models. These effects were associated with cell-cycle arrest and modulation of related proteins (cyclin D1, cyclin E, p27, and p21), all target genes of FoxO3a, an ubiquitous transcription factor negatively regulated by AKT. Lamotrigine also increases the expression of another FoxO3a target, PTEN, which, in turn, downregulates the PI3K/Akt signaling pathway, with consequent dephosphorylation, thus activation, of FoxO3a. Moreover, lamotrigine induces FoxO3a expression by increasing its transcription through FoxO3a recruitment on specific FHRE located on its own promoter, in an autoregulatory fashion. Finally, lamotrigine significantly reduced tumor growth , increasing FoxO3a expression. The anticonvulsant drug lamotrigine shows strong antiproliferative activity on breast cancer, both and Thus, drug repurposing could represent a valuable option for a molecularly targeted therapy in breast cancer patients. .

show abstract

“…Androgen independent cancer evolves from genetic mutations within the cell that allow it to grow independent of AR activity; instead it follows pathways involving overexpression of BCL2 or inactivation of tumor suppressor genes among many others (Brooke & Bevan, 2009;Cattrini et al, 2017). These pathways have also been linked to other hormone independent cancers such as breast cancer (Bullock, 2016).…”

Section: The Role Of Sgta In Prostate Cancermentioning

confidence: 99%