Investigating senescence and senescence-escape in cancer cells (2022)
Thesis
Toth, F. (2022). Investigating senescence and senescence-escape in cancer cells. (Thesis). University of Salford

Despite the general concept that therapy-induced senescence (TIS) has a tumour-suppressive role, the presence of senescent tumour cells and the ability of cancer cells to escape from senescence could potentially lead to therapy resistance and tumour... Read More about Investigating senescence and senescence-escape in cancer cells.

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
Sargiacomo, C., Stonehouse, S., Moftakhar, Z., Sotgia, F., & Lisanti, M. (2021). 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. Frontiers in Oncology, 11, 678343. https://doi.org/10.3389/fonc.2021.678343

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.

FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer (2019)
Journal Article
Pellegrino, M., Rizza, P., Donà, A., Nigro, A., Ricci, E., Fiorillo, M., …Morelli, C. (2019). FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer. Cancers, 11(12), e1858. https://doi.org/10.3390/cancers11121858

Background: Resistance to endocrine treatments is a major clinical challenge in the management of estrogen receptor positive breast cancers. Although multiple mechanisms leading to endocrine resistance have been proposed, the poor outcome of this sub... Read More about FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer.

Thioalbamide, a thioamidated peptide from amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress (2019)
Journal Article
Frattaruolo, L., Fiorillo, M., Brindisi, M., Curcio, R., Dolce, V., Lacret, R., …Cappello, A. (2019). Thioalbamide, a thioamidated peptide from amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress. Cells, 8(11), e1408. https://doi.org/10.3390/cells8111408

Thioalbamide, a thioamidated peptide biosynthesized by Amycolatopsis alba, is a thioviridamide-like molecule, and is part of a family of natural products representing a focus of biotechnological and pharmaceutical research in recent years due to thei... Read More about Thioalbamide, a thioamidated peptide from amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress.

Doxycycline, Azithromycin and vitamin C (DAV) : a potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs) (2019)
Journal Article
Fiorillo, M., Tóth, F., Sotgia, F., & Lisanti, M. (2019). Doxycycline, Azithromycin and vitamin C (DAV) : a potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs). Aging, 11(8), 2202-2216. https://doi.org/10.18632/aging.101905

Here, we devised a new strategy for eradicating cancer stem cells (CSCs), via a "synthetic-metabolic" approach, involving two FDA-approved antibiotics and a dietary vitamin supplement. This approach was designed to induce a "rho-zero-like" phenotype... Read More about Doxycycline, Azithromycin and vitamin C (DAV) : a potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs).

Hallmarks of the cancer cell of origin : comparisons with "energetic" cancer stem cells (e-CSCs) (2019)
Journal Article
Sotgia, F., Fiorillo, M., & Lisanti, M. (2019). Hallmarks of the cancer cell of origin : comparisons with "energetic" cancer stem cells (e-CSCs). Aging, 11(3), 1065-1068. https://doi.org/10.18632/aging.101822

Here, we discuss the expected hallmark(s) of the cancer cell of origin and how this may be related to a new tumor cell phenotype, namely "energetic" cancer stem cells (e-CSCs). e-CSCs show many features that would be characteristic of the cancer cell... Read More about Hallmarks of the cancer cell of origin : comparisons with "energetic" cancer stem cells (e-CSCs).

“Energetic” cancer stem cells (e-CSCs) : a new hyper-metabolic and proliferative tumor cell phenotype, driven by mitochondrial energy (2019)
Journal Article
Fiorillo, M., Sotgia, F., & Lisanti, M. (2019). “Energetic” cancer stem cells (e-CSCs) : a new hyper-metabolic and proliferative tumor cell phenotype, driven by mitochondrial energy. Frontiers in Oncology, 8(677), https://doi.org/10.3389/fonc.2018.00677

Here, we provide the necessary evidence that mitochondrial metabolism drives the anchorage-independent proliferation of CSCs. Two human breast cancer cell lines, MCF7 [ER(+)] and MDA-MB-468 (triple-negative), were used as model systems. To directly... Read More about “Energetic” cancer stem cells (e-CSCs) : a new hyper-metabolic and proliferative tumor cell phenotype, driven by mitochondrial energy.

The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling : implicating TIGAR in somatic resistance to endocrine therapy (2018)
Journal Article
Fiorillo, M., Sanchez-Alvarez, R., Sotgia, F., & Lisanti, M. (2018). The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling : implicating TIGAR in somatic resistance to endocrine therapy. Aging, 10(12), 4000-4023. https://doi.org/10.18632/aging.101690

Naturally-occurring somatic mutations in the estrogen receptor gene (ESR1) have been previously implicated in the clinical development of resistance to hormonal therapies, such as Tamoxifen. For example, the somatic mutation Y537S has been specifical... Read More about The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling : implicating TIGAR in somatic resistance to endocrine therapy.

Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts (2018)
Journal Article
Ozsvari, B., Nuttall, J., Sotgia, F., & Lisanti, M. (2018). Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts. Aging, 10(11), 3294-3307. https://doi.org/10.18632/aging.101633

Here, we employed a “senolytic” assay system as a screening tool, with the goal of identifying and repurposing FDA-approved antibiotics, for the targeting of the senescent cell population. Briefly, we used two established human fibroblast cell lines... Read More about Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts.

Doxycycline, an inhibitor of mitochondrial biogenesis, effectively reduces cancer stem cells (CSCs) in early breast cancer patients : a clinical pilot study (2018)
Journal Article
Scatena, C., Roncella, M., Di Paolo, A., Aretini, P., Menicagli, M., Fanelli, G., …Naccarato, A. (2018). Doxycycline, an inhibitor of mitochondrial biogenesis, effectively reduces cancer stem cells (CSCs) in early breast cancer patients : a clinical pilot study. Frontiers in Oncology, 8(452), https://doi.org/10.3389/fonc.2018.00452

Background and objectives: Cancer stem cells (CSCs) have been implicated in tumor initiation, recurrence, metastatic spread and poor survival in multiple tumor types, breast cancers included. CSCs selectively overexpress key mitochondrial-related pro... Read More about Doxycycline, an inhibitor of mitochondrial biogenesis, effectively reduces cancer stem cells (CSCs) in early breast cancer patients : a clinical pilot study.

A mitochondrial based oncology platform for targeting cancer stem cells (CSCs) : MITO-ONC-RX (2018)
Journal Article
Sotgia, F., Ozsvari, B., Fiorillo, M., De Francesco, E., Bonuccelli, G., & Lisanti, M. (2018). A mitochondrial based oncology platform for targeting cancer stem cells (CSCs) : MITO-ONC-RX. Cell Cycle, 17(17), 2091-2100. https://doi.org/10.1080/15384101.2018.1515551

Here, we wish to propose a new systematic approach to cancer therapy, based on the targeting of mitochondrial metabolism, especially in cancer stem cells (CSCs). In the future, we envision that anti-mitochondrial therapy would ultimately be practiced... Read More about A mitochondrial based oncology platform for targeting cancer stem cells (CSCs) : MITO-ONC-RX.

Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways (2018)
Journal Article
Bonuccelli, G., Sotgia, F., & Lisanti, M. (2018). Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways. Aging, 10(8), 1867-1883. https://doi.org/10.18632/aging.101483

Matcha green tea (MGT) is a natural product that is currently used as a dietary supplement and may have significant anti-cancer properties. However, the molecular mechanism(s) underpinning its potential health benefits remain largely unknown. Here, w... Read More about Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways.

Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication (2018)
Journal Article
De Francesco, E., Sotgia, F., & Lisanti, M. (2018). Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication. Biochemical Journal, 475(9), 1611-1634. https://doi.org/10.1042/BCJ20170164

Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that... Read More about Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication.

Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism (2018)
Journal Article
Fiorillo, M., Peiris-Pagès, M., Sanchez-Alvarez, R., Bartella, L., Di Donna, L., Dolce, V., …Lisanti, M. (2018). Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism. BBA - Bioenergetics, 1859(9), 984-996. https://doi.org/10.1016/j.bbabio.2018.03.018

Here, we show that a 2:1 mixture of Brutieridin and Melitidin, termed “BMF”, has a statin-like properties, which blocks the action of the rate-limiting enzyme for mevalonate biosynthesis, namely HMGR (3-hydroxy-3-methylglutaryl- CoA-reductase). Mor... Read More about Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism.

Exploiting mitochondrial targeting signal(s), TPP and bis-TPP, for eradicating cancer stem cells (CSCs) (2018)
Journal Article
Ozsvari, B., Sotgia, F., & Lisanti, M. (2018). Exploiting mitochondrial targeting signal(s), TPP and bis-TPP, for eradicating cancer stem cells (CSCs). Aging, 10(2), 229-240. https://doi.org/10.18632/aging.101384

Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally behaves as a mitochondrial targeting signal (MTS) in living cells. Here, we explored the hypothesis that TPP-related compounds could be utilized to inhibit mitochondria in... Read More about Exploiting mitochondrial targeting signal(s), TPP and bis-TPP, for eradicating cancer stem cells (CSCs).

Mitochondrial fission as a driver of stemness in tumor cells : mDIVI1 inhibits mitochondrial function, cell migration and cancer stem cell (CSC) signalling (2018)
Journal Article
Peiris-Pagès, M., Bonuccelli, G., Sotgia, F., & Lisanti, M. (2018). Mitochondrial fission as a driver of stemness in tumor cells : mDIVI1 inhibits mitochondrial function, cell migration and cancer stem cell (CSC) signalling. Oncotarget, 9(17), 13254-13275. https://doi.org/10.18632/oncotarget.24285

Mitochondria are dynamic organelles frequently undergoing fission and fusion events to maintain their integrity, bioenergetics and spatial distribution, which is fundamental to the processes of cell survival. Disruption in mitochondrial dynamics play... Read More about Mitochondrial fission as a driver of stemness in tumor cells : mDIVI1 inhibits mitochondrial function, cell migration and cancer stem cell (CSC) signalling.

G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis : old paradigms and emerging concepts (2017)
Journal Article
De Francesco, E., Sotgia, F., Clarke, R., Lisanti, M., & Maggiolini, M. (2017). G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis : old paradigms and emerging concepts. International Journal of Molecular Sciences, 18(12), https://doi.org/10.3390/ijms18122713

G protein-coupled receptors (GPCRs) have been implicated in transmitting signals across the extra- and intra-cellular compartments, thus allowing environmental stimuli to elicit critical biological responses. As GPCRs can be activated by an extensive... Read More about G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis : old paradigms and emerging concepts.

GPER mediates the angiocrine actions induced by IGF1 through the HIF-1α/VEGF pathway in the breast tumor microenvironment (2017)
Journal Article
De Francesco, E., Sims, A., Maggiolini, M., Sotgia, F., Lisanti, M., & Clarke, R. (2017). GPER mediates the angiocrine actions induced by IGF1 through the HIF-1α/VEGF pathway in the breast tumor microenvironment. Breast Cancer Research, 19(1), 129. https://doi.org/10.1186/s13058-017-0923-5

The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional ta... Read More about GPER mediates the angiocrine actions induced by IGF1 through the HIF-1α/VEGF pathway in the breast tumor microenvironment.

Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer (2017)
Journal Article
Monti, D., Sotgia, F., Whitaker-Menezes, D., Tuluc, M., Birbe, R., Berger, A., …Martinez-Outschoorn, U. (2017). Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer. Seminars in Oncology, 44(3), 226-232. https://doi.org/10.1053/j.seminoncol.2017.10.001

Background High oxidative stress as defined by hydroxyl and peroxyl activity is often found in the stroma of human breast cancers. Oxidative stress induces stromal catabolism, which promotes cancer aggressiveness. Stromal cells exposed to oxidativ... Read More about Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer.