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ALDHHigh Breast Cancer Stem Cells Exhibit a Mesenchymal–Senescent Hybrid Phenotype, with Elevated Metabolic and Migratory Activities (2024)
Journal Article
Larrea Murillo, L., Sugden, C. J., Ozsvari, B., Moftakhar, Z., Hassan, G. S., Sotgia, F., & Lisanti, M. P. (in press). ALDHHigh Breast Cancer Stem Cells Exhibit a Mesenchymal–Senescent Hybrid Phenotype, with Elevated Metabolic and Migratory Activities. Cells, 13(24), 2059. https://doi.org/10.3390/cells13242059

Cancer stem cells (CSCs) account for 0.01 to 2% of the total tumor mass; however, they play a key role in tumor progression, metastasis and resistance to current cancer therapies. The generation and maintenance of CSCs are usually linked to the epith... Read More about ALDHHigh Breast Cancer Stem Cells Exhibit a Mesenchymal–Senescent Hybrid Phenotype, with Elevated Metabolic and Migratory Activities.

High mitochondrial DNA content is a key determinant of stemness, proliferation, cell migration, and cancer metastasis in vivo (2024)
Journal Article
Mauro-Lizcano, M., Di Pisa, F., Larrea Murillo, L., Sugden, C. J., Sotgia, F., & Lisanti, M. P. (in press). High mitochondrial DNA content is a key determinant of stemness, proliferation, cell migration, and cancer metastasis in vivo. Cell Death and Disease, 15(10), Article 745. https://doi.org/10.1038/s41419-024-07103-9

Here, we examined the potential role of mitochondrial DNA (mtDNA) levels in conveying aggressive phenotypes in cancer cells, using two widely-used breast cell lines as model systems (MCF7[ER+] and MDA-MB-231[ER-]). These human breast cancer cell line... Read More about High mitochondrial DNA content is a key determinant of stemness, proliferation, cell migration, and cancer metastasis in vivo.

Mitophagy and cancer: role of BNIP3/BNIP3L as energetic drivers of stemness features, ATP production, proliferation, and cell migration (2024)
Journal Article
Mauro-Lizcano, M., Sotgia, F., & Lisanti, M. P. (in press). Mitophagy and cancer: role of BNIP3/BNIP3L as energetic drivers of stemness features, ATP production, proliferation, and cell migration. Aging, 16(11), 9334—9349. https://doi.org/10.18632/aging.205939

Mitophagy is a selective form of autophagy which permits the removal of dysfunctional or excess mitochondria. This occurs as an adaptative response to physiological stressors, such as hypoxia, nutrient deprivation, or DNA damage. Mitophagy is promote... Read More about Mitophagy and cancer: role of BNIP3/BNIP3L as energetic drivers of stemness features, ATP production, proliferation, and cell migration.

In Vitro Investigation of Therapy-Induced Senescence and Senescence Escape in Breast Cancer Cells Using Novel Flow Cytometry-Based Methods (2024)
Journal Article
Tóth, F., Moftakhar, Z., Sotgia, F., & Lisanti, M. P. (in press). In Vitro Investigation of Therapy-Induced Senescence and Senescence Escape in Breast Cancer Cells Using Novel Flow Cytometry-Based Methods. Cells, 13(10), 841. https://doi.org/10.3390/cells13100841

Although cellular senescence was originally defined as an irreversible form of cell cycle arrest, in therapy-induced senescence models, the emergence of proliferative senescence-escaped cancer cells has been reported by several groups, challenging th... Read More about In Vitro Investigation of Therapy-Induced Senescence and Senescence Escape in Breast Cancer Cells Using Novel Flow Cytometry-Based Methods.

FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity (2023)
Journal Article

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 acquisi... Read More about FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity.

Antibiotics that target mitochondria extend lifespan in C. elegans (2023)
Journal Article
Bonuccelli, G., Brooks, D. R., Shepherd, S., Sotgia, F., Lisanti, M. P., Brooks, D. R., & Lisanti, M. P. (in press). Antibiotics that target mitochondria extend lifespan in C. elegans. Aging, 15(21), 11764-11781. https://doi.org/10.18632/aging.205229

Aging is a continuous degenerative process caused by a progressive decline of cell and tissue functions in an organism. It is induced by the accumulation of damage that affects normal cellular processes, ultimately leading to cell death. It has been... Read More about Antibiotics that target mitochondria extend lifespan in C. elegans.

SOX2-high cancer cells exhibit an aggressive phenotype, with increases in stemness, proliferation and invasion, as well as higher metabolic activity and ATP production (2022)
Journal Article
Mauro Lizcano, M., Sotgia, F., & Lisanti, M. (2022). SOX2-high cancer cells exhibit an aggressive phenotype, with increases in stemness, proliferation and invasion, as well as higher metabolic activity and ATP production. Aging, 14(24), 9877-9889. https://doi.org/10.18632/aging.204452

Cancer stem cells (CSCs) are responsible for cancer recurrence, treatment failure and metastatic dissemination. As such, the elimination of CSCs represents one of the most important approaches for the future of cancer treatment. Among other propertie... Read More about SOX2-high cancer cells exhibit an aggressive phenotype, with increases in stemness, proliferation and invasion, as well as higher metabolic activity and ATP production.

Identification of natural products and FDA-approved drugs for targeting cancer stem cell (CSC) propagation (2022)
Journal Article
Bonuccelli, G., Sotgia, F., & Lisanti, M. (2022). Identification of natural products and FDA-approved drugs for targeting cancer stem cell (CSC) propagation. Aging, 14(23), 9466-9483. https://doi.org/10.18632/aging.204412

Here, we report the identification of key compounds that effectively inhibit the anchorage-independent growth and propagation of cancer stem cells (CSCs), as determined via screening using MCF7 cells, a human breast adenocarcinoma cell line. More spe... Read More about Identification of natural products and FDA-approved drugs for targeting cancer stem cell (CSC) propagation.

New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration. (2022)
Journal Article
Brindisi, M., Frattaruolo, L., Fiorillo, M., Dolce, V., Sotgia, F., Lisanti, M., & Cappello, A. (2022). New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration. FEBS Journal, https://doi.org/10.1111/febs.16651

Breast cancer remains the greatest cause of cancer-related death in women worldwide. Its aggressiveness and progression derive from intricate processes that occur simultaneously both within the tumour itself and in the neighbouring cells that make up... Read More about New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration..

High ATP production fuels cancer drug resistance and metastasis : implications for mitochondrial ATP depletion therapy (2021)
Journal Article
Fiorillo, M., Ozsvari, B., Sotgia, F., & Lisanti, M. (2021). High ATP production fuels cancer drug resistance and metastasis : implications for mitochondrial ATP depletion therapy. Frontiers in Oncology, 11, 740720. https://doi.org/10.3389/fonc.2021.740720

Recently, we presented evidence that high mitochondrial ATP production is a new therapeutic target for cancer treatment. Using ATP as a biomarker, we isolated the “metabolically fittest” cancer cells from the total cell population. Importantly, ATP-h... Read More about High ATP production fuels cancer drug resistance and metastasis : implications for mitochondrial ATP depletion therapy.

MitoTracker Deep Red (MTDR) is a metabolic inhibitor for targeting mitochondria and eradicating cancer stem cells (CSCs), with anti-tumor and anti-metastatic activity in vivo (2021)
Journal Article

MitoTracker Deep Red (MTDR) is a relatively non-toxic, carbocyanine-based, far-red, fluorescent probe that is routinely used to
chemically mark and visualize mitochondria in living cells. Previously, we used MTDR at low nano-molar concentrations to... Read More about MitoTracker Deep Red (MTDR) is a metabolic inhibitor for targeting mitochondria and eradicating cancer stem cells (CSCs), with anti-tumor and anti-metastatic activity in vivo.

Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase (2021)
Journal Article
Fiorillo, M., Scatena, C., Naccarato, A., Sotgia, F., & Lisanti, M. (2021). Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase. Cell Death and Differentiation, 28(9), 2797-2817. https://doi.org/10.1038/s41418-021-00788-x

Here, we provide evidence that high ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anticancer therapy, especially for preventing tumor progression. More specifically, we isolated a subpopulation of ATP-high cancer ce... Read More about Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase.

Mitochondrial Fission Factor (MFF) inhibits mitochondrial metabolism and reduces breast cancer stem cell (CSC) activity (2020)
Journal Article
Sánchez-Alvarez, R., De Francesco, E., Fiorillo, M., Sotgia, F., & Lisanti, M. (2020). Mitochondrial Fission Factor (MFF) inhibits mitochondrial metabolism and reduces breast cancer stem cell (CSC) activity. Frontiers in Oncology, 10, 1776. https://doi.org/10.3389/fonc.2020.01776

Elevated mitochondrial biogenesis and metabolism represent key features of breast cancer stem cells (CSCs), whose propagation is conducive to disease onset and progression. Therefore, interfering with mitochondria biology and function may be regarded... Read More about Mitochondrial Fission Factor (MFF) inhibits mitochondrial metabolism and reduces breast cancer stem cell (CSC) activity.

Using the common cold virus as a naturally occurring vaccine to prevent COVID-19 : lessons from Edward Jenner (2020)
Journal Article
Sotgia, F., & Lisanti, M. (2020). Using the common cold virus as a naturally occurring vaccine to prevent COVID-19 : lessons from Edward Jenner. Aging, 12(19), 18797-18803. https://doi.org/10.18632/aging.104166

Three recent papers published in Nature, Science and Cell, all present clear evidence that there is cross-reactive T-cell immunity between human coronaviruses (229E, NL63, OC43, and HKU1), linked with the common cold, and SARS-CoV-2, the causative ag... Read More about Using the common cold virus as a naturally occurring vaccine to prevent COVID-19 : lessons from Edward Jenner.

A myristoyl amide derivative of doxycycline potently targets cancer stem cells (CSCs) and prevents metastasis, without retaining antibiotic activity (2020)
Journal Article

Here, we describe the chemical synthesis and biological activity of a new Doxycycline derivative, designed specifically to more effectively target cancer stem cells (CSCs). In this analogue, a myristic acid (14 carbon) moiety is covalently attached t... Read More about A myristoyl amide derivative of doxycycline potently targets cancer stem cells (CSCs) and prevents metastasis, without retaining antibiotic activity.

Cholesterol and mevalonate : two metabolites involved in breast cancer progression and drug resistance through the ERRα pathway (2020)
Journal Article
Brindisi, M., Fiorillo, M., Frattaruolo, L., Sotgia, F., Lisanti, M., & Cappello, A. (2020). Cholesterol and mevalonate : two metabolites involved in breast cancer progression and drug resistance through the ERRα pathway. Cells, 9(8), e1819. https://doi.org/10.3390/cells9081819

Breast cancer is the second greatest cause of cancer-related death in women. Resistance to endocrine treatments or chemotherapy is a limiting drawback. In this context, this work aims to evaluate the effects of cholesterol and mevalonate during tumor... Read More about Cholesterol and mevalonate : two metabolites involved in breast cancer progression and drug resistance through the ERRα pathway.

Essential role of STAT5a in DCIS formation and invasion following estrogen treatment (2020)
Journal Article
Dees, S., Pontiggia, L., Jasmin, J., Sotgia, F., Lisanti, M., & Mercier, I. (2020). Essential role of STAT5a in DCIS formation and invasion following estrogen treatment. Aging, 12(14), 15104-15120. https://doi.org/10.18632/aging.103586

Ductal carcinoma in situ (DCIS) is one of the earliest stages of breast cancer (BCa). The mechanisms by which DCIS lesions progress to an invasive state while others remain indolent are yet to be fully characterized and both diagnosis and treatment o... Read More about Essential role of STAT5a in DCIS formation and invasion following estrogen treatment.

Deferiprone (DFP) targets cancer stem cell (CSC) propagation by inhibiting mitochondrial metabolism and inducing ROS production (2020)
Journal Article
Fiorillo, M., Tóth, F., Brindisi, M., Sotgia, F., & Lisanti, M. (2020). Deferiprone (DFP) targets cancer stem cell (CSC) propagation by inhibiting mitochondrial metabolism and inducing ROS production. Cells, 9(6), e1529. https://doi.org/10.3390/cells9061529

Deferiprone (DFP), also known as Ferriprox, is an FDA-approved, orally active, iron chelator that is currently used clinically for the treatment of iron-overload, especially in thalassaemia major. As iron is a critical factor in Fe-S cluster assembly... Read More about Deferiprone (DFP) targets cancer stem cell (CSC) propagation by inhibiting mitochondrial metabolism and inducing ROS production.

First-in-class candidate therapeutics that target mitochondria and effectively prevent cancer cell metastasis : mitoriboscins and TPP compounds (2020)
Journal Article
Ozsvari, B., Sotgia, F., & Lisanti, M. (2020). First-in-class candidate therapeutics that target mitochondria and effectively prevent cancer cell metastasis : mitoriboscins and TPP compounds. Aging, 12(11), 10162-10179. https://doi.org/10.18632/aging.103336

Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence, distant metastasis and drug-resistance, in the vast majority of cancer patients. Therefore, there is an urgent need to identify new drugs that can target and eradicat... Read More about First-in-class candidate therapeutics that target mitochondria and effectively prevent cancer cell metastasis : mitoriboscins and TPP compounds.