Forkhead-Box (Fox)O Family Transcription Factors in Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: 15 June 2024 | Viewed by 1366

Special Issue Editors


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Guest Editor
Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: growth factor signaling in solid tumors and metastasis; growth factor/steroid hormone crosstalk in hormone-dependent tumors; growth factors signaling proteins as markers of breast cancer progression; role of forkhead-box transcription factor 3a (FoxO3a) in the tumorigenesis and progression of breast cancer; mechanisms of resistance to endocrine therapy in breast cancer; multifunctional mesoporous silica nanoparticles as innovative devices for targeted therapy

E-Mail Website
Guest Editor
Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: role of the androgen receptor in hormone-dependent tumor growth and progression; molecular mechanisms underlying the functional crosstalk between estrogens, androgens, and growth factors in breast cancer; regulation of aromatase enzyme activity in the male gonad and in breast cancer cell lines

Special Issue Information

Dear Colleagues,

As Guest Editors of the Journal Cells (IF 7,666), we have the privilege to invite you to contribute a review or original article to the Special Issue “Forkhead-box (Fox) O Family Transcription Factors in Cancer”.

Forkhead-box class O (FoxO) family members FoxO1a, FoxO3a, FoxO4, and FoxO6 are nuclear transcription factors that control diverse biological processes, affecting development, metabolism, stem cell maintenance, and longevity. They have also been increasingly recognized as tumor suppressors for their ability to regulate the expression of genes involved in cell proliferation, DNA repair, apoptosis, angiogenesis, cell migration, and metastasis. Thus, deregulation of FoxOs expression and function has been associated with cancer initiation, progression, and drug resistance. However, several other studies have shown that FoxOs might also promote tumor progression in certain circumstances.

Therefore, this SI is aimed at deepening the understanding on FoxOs regulation and functions in cancer as well as in normal tissues, in order to clarify their prognostic value in various subsets of tumors and, at the same time, pave the way to more effective treatment options, exploiting FoxOs as targetable factors in cancer therapy.

Dr. Catia Morelli
Prof. Marilena Lanzino
Guest Editors

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Keywords

  • forkhead-box class O transcription factors
  • cancer
  • apoptosis
  • tumor progression
  • EMT
  • gene transcription
  • drug resistance
  • endocrine therapy
  • lnRNA
  • PTMs

Published Papers (1 paper)

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Research

18 pages, 5539 KiB  
Article
FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity
by Marco Fiorillo, Elena Ricci, Mariarosa Fava, Camilla Longobucco, Federica Sotgia, Pietro Rizza, Marilena Lanzino, Daniela Bonofiglio, Francesca Luisa Conforti, Stefania Catalano, Ines Barone, Catia Morelli, Saveria Aquila, Michael P. Lisanti and Diego Sisci
Cells 2023, 12(24), 2777; https://doi.org/10.3390/cells12242777 - 06 Dec 2023
Viewed by 1105
Abstract
Tamoxifen-resistant breast cancer cells (TamR-BCCs) are characterized by an enhanced metabolic phenotype compared to tamoxifen-sensitive cells. FoxO3a is an important modulator of cell metabolism, and its deregulation has been involved in the acquisition of tamoxifen resistance. Therefore, tetracycline-inducible FoxO3a was overexpressed in TamR-BCCs [...] Read more.
Tamoxifen-resistant breast cancer cells (TamR-BCCs) are characterized by an enhanced metabolic phenotype compared to tamoxifen-sensitive cells. FoxO3a is an important modulator of cell metabolism, and its deregulation has been involved in the acquisition of tamoxifen resistance. Therefore, tetracycline-inducible FoxO3a was overexpressed in TamR-BCCs (TamR/TetOn-AAA), which, together with their control cell line (TamR/TetOn-V), were subjected to seahorse metabolic assays and proteomic analysis. FoxO3a was able to counteract the increased oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) observed in TamR by reducing their energetic activity and glycolytic rate. FoxO3a caused glucose accumulation, very likely by reducing LDH activity and mitigated TamR biosynthetic needs by reducing G6PDH activity and hindering NADPH production via the pentose phosphate pathway (PPP). Proteomic analysis revealed a FoxO3a-dependent marked decrease in the expression of LDH as well as of several enzymes involved in carbohydrate metabolism (e.g., Aldolase A, LDHA and phosphofructokinase) and the analysis of cBioPortal datasets of BC patients evidenced a significant inverse correlation of these proteins and FoxO3a. Interestingly, FoxO3a also increased mitochondrial biogenesis despite reducing mitochondrial functionality by triggering ROS production. Based on these findings, FoxO3a inducing/activating drugs could represent promising tools to be exploited in the management of patients who are refractory to antiestrogen therapy. Full article
(This article belongs to the Special Issue Forkhead-Box (Fox)O Family Transcription Factors in Cancer)
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