Dissecting tumor metabolic heterogeneity : Telomerase and large cell size metabolically define a sub-population of stem-like, mitochondrial-rich, cancer cells

Lamb, R; Ozsvari, B; Bonuccelli, G; Smith, D; Pestell, R; Martinez-Outschoorn, U; Clarke, R; Sotgia, Federica; Lisanti, MP

doi:10.18632/oncotarget.5260

Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer : companion diagnostics for cancer therapy (2017)
Journal Article
Sotgia, F., & Lisanti, M. (2017). Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer : companion diagnostics for cancer therapy. Oncotarget, 8(40), 66925-66939. https://doi.org/10.18632/oncotarget.19963

Here, we performed a systematic analysis to discover new biomarkers of overall survival and tumor progression in ovarian cancer patients. More specifically, we determined whether nuclear-encoded mitochondrial genes related to mitochondrial biogenesis... Read More about Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer : companion diagnostics for cancer therapy.

Mitochondrial biomarkers predict tumor progression and poor overall survival in gastric cancers : companion diagnostics for personalized medicine. (2017)
Journal Article
Sotgia, F., & Lisanti, M. (2017). Mitochondrial biomarkers predict tumor progression and poor overall survival in gastric cancers : companion diagnostics for personalized medicine. Oncotarget, 8(40), 67117-67128. https://doi.org/10.18632/oncotarget.19962

Here, we employed a bioinformatics approach to identify novel molecular determinants to predict tumor progression and overall survival in gastric cancer patients. In particular, we directly assessed whether nuclear-derived mRNA species encoding prote... Read More about Mitochondrial biomarkers predict tumor progression and poor overall survival in gastric cancers : companion diagnostics for personalized medicine..

Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients : use as companion diagnostics (2017)
Journal Article
Sotgia, F., & Lisanti, M. (2017). Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients : use as companion diagnostics. Oncotarget, 8(40), 68095-68107. https://doi.org/10.18632/oncotarget.19677

Here, we used an informatics-based approach to identify novel biomarkers of overall survival and tumor progression in non-small cell lung cancer (NSCLC) patients. We determined whether nuclear-encoded genes associated with mitochondrial biogenesis an... Read More about Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients : use as companion diagnostics.

Mitochondrial markers predict recurrence, metastasis and Tamoxifen-resistance in breast cancer patients : early detection of treatment failure with companion diagnostics (2017)
Journal Article
Sotgia, F., Fiorillo, M., & Lisanti, M. (2017). Mitochondrial markers predict recurrence, metastasis and Tamoxifen-resistance in breast cancer patients : early detection of treatment failure with companion diagnostics. Oncotarget, 2017(8), 68730-68745. https://doi.org/10.18632/oncotarget.19612

Here, we used a data-mining and informatics approach to discover new biomarkers of resistance to hormonal therapy in breast cancer. More specifically, we investigated whether nuclear-encoded genes associated with mitochondrial biogenesis can be used... Read More about Mitochondrial markers predict recurrence, metastasis and Tamoxifen-resistance in breast cancer patients : early detection of treatment failure with companion diagnostics.

Mitoriboscins : mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast (2017)
Journal Article
Ozsvari, B., Fiorillo, M., Bonuccelli, G., Cappello, A., Frattaruolo, L., Sotgia, F., …Lisanti, M. (2017). Mitoriboscins : mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast. Oncotarget, 2017(8), 67457-67472. https://doi.org/10.18632/oncotarget.19084

The “endo-symbiotic theory of mitochondrial evolution” states that mitochondrial organelles evolved from engulfed aerobic bacteria, after millions of years of symbiosis and adaptation. Here, we have exploited this premise to design new antibiotics an... Read More about Mitoriboscins : mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast.

Targeting hypoxic cancer stem cells (CSCs) with Doxycycline : implications for optimizing anti-angiogenic therapy (2017)
Journal Article
implications for optimizing anti-angiogenic therapy. Oncotarget, 2017(8), 56126-56142. https://doi.org/10.18632/oncotarget.18445

Here, we report new mechanistic insight into how chronic hypoxia increases ‘stemness’ in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypox... Read More about Targeting hypoxic cancer stem cells (CSCs) with Doxycycline : implications for optimizing anti-angiogenic therapy.

Vitamin C and Doxycycline : a synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs) (2017)
Journal Article
De Francesco, E., Bonuccelli, G., Maggiolini, M., Sotgia, F., & Lisanti, M. (2017). Vitamin C and Doxycycline : a synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs). Oncotarget, 2017(8), 67269-67286. https://doi.org/10.18632/oncotarget.18428

Here, we developed a new synthetic lethal strategy for further optimizing the eradication of cancer stem cells (CSCs). Briefly, we show that chronic treatment with the FDA-approved antibiotic Doxycycline effectively reduces cellular respiration, by... Read More about Vitamin C and Doxycycline : a synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs).

Hodgkin lymphoma : a complex metabolic ecosystem with glycolytic reprogramming of the tumor microenvironment (2017)
Journal Article
Mikkilineni, L., Whitaker-Menezes, D., Domingo-Vidal, M., Sprandio, J., Avena, P., Cotzia, P., …Martinez-Outschoorn, U. (2017). Hodgkin lymphoma : a complex metabolic ecosystem with glycolytic reprogramming of the tumor microenvironment. Seminars in Oncology, 44(3), 218-225. https://doi.org/10.1053/j.seminoncol.2017.10.003

Background Twenty percent of patients with classical Hodgkin Lymphoma (cHL) have aggressive disease defined as relapsed or refractory disease to initial therapy. At present we cannot identify these patients pre-treatment. The microenvironment is v... Read More about Hodgkin lymphoma : a complex metabolic ecosystem with glycolytic reprogramming of the tumor microenvironment.

Current and prospective pharmacotherapies for the treatment of pleural mesothelioma (2017)
Journal Article
Bakker, E., Guazzelli, A., Krstic-Demonacos, M., Lisanti, M., Sotgia, F., & Mutti, L. (2017). Current and prospective pharmacotherapies for the treatment of pleural mesothelioma. Expert Opinion on Orphan Drugs, 5(6), 455-465. https://doi.org/10.1080/21678707.2017.1325358

Introduction: Mesothelioma is a rare asbestos-linked cancer with an expected incidence peak between 2015–2030. Therapies remain ineffective, thus developing and testing novel treatments is important for both oncologists and researchers. Areas co... Read More about Current and prospective pharmacotherapies for the treatment of pleural mesothelioma.

Mitochondrial “power” drives tamoxifen resistance : NQO1 and GCLC are new therapeutic targets in breast cancer (2017)
Journal Article
Fiorillo, M., Sotgia, F., Sisci, D., Cappello, A., & Lisanti, M. (2017). Mitochondrial “power” drives tamoxifen resistance : NQO1 and GCLC are new therapeutic targets in breast cancer. Oncotarget, 2017(8), 20309-20327. https://doi.org/10.18632/oncotarget.15852

Here, we identified two new molecular targets, which are functionally sufficient to metabolically confer the tamoxifen-resistance phenotype in human breast cancer cells. Briefly, ~20 proteins were first selected as potential candidates, based on u... Read More about Mitochondrial “power” drives tamoxifen resistance : NQO1 and GCLC are new therapeutic targets in breast cancer.

Anti-CTLA-4 therapy for malignant mesothelioma (2017)
Journal Article
Guazzelli, A., Bakker, E., Krstic-Demonacos, M., Lisanti, M., Sotgia, F., & Mutti, L. (2017). Anti-CTLA-4 therapy for malignant mesothelioma. Immunotherapy, 9(3), 273-280. https://doi.org/10.2217/imt-2016-0123

Immunotherapy is an emerging therapeutic strategy with a promising clinical outcome in some solid tumors, particularly metastatic melanoma. One approach to immunotherapy is immune checkpoint inhibitors, such as blockage of CTLA-4 and PD-1/PD-L1. This... Read More about Anti-CTLA-4 therapy for malignant mesothelioma.

Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity (2016)
Journal Article
Bonuccelli, G., Peires-Pages, M., Ozsvari, B., Martinez- Outschoorn, U., Sotgia, F., & Lisanti, M. (2017). Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity. Oncotarget, 8(6), 9868-9884. https://doi.org/10.18632/oncotarget.14196

In this report, we systematically examined the role of telomerase activity in lung and ovarian cancer stem cell (CSC) propagation. For this purpose, we indirectly gauged telomerase activity, by linking the hTERT-promoter to eGFP. Using lung (A549)... Read More about Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity.

Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs) (2016)
Journal Article
Fiorillo, M., Lamb, R., Tanowitz, H., Cappello, A., Martinez‐Outschoorn, U., Sotgia, F., & Lisanti, M. (2016). Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs). Aging, 8(8), 1593-1607. https://doi.org/10.18632/aging.100983

Bedaquiline (a.k.a., Sirturo) is an anti‐microbial agent, which is approved by the FDA for the treatment of multi‐drug resistant pulmonary tuberculosis (TB). Bedaquiline is a first‐in‐class diaryl‐quinoline compound, that mechanistically inhibits the... Read More about Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs).

Cancer stem cell metabolism (2016)
Journal Article
Peiris-Pagès, M., Martinez-Outschoorn, U., Pestell, R., Sotgia, F., & Lisanti, M. (2016). Cancer stem cell metabolism. Breast Cancer Research, 18(55), https://doi.org/10.1186/s13058-016-0712-6

Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as... Read More about Cancer stem cell metabolism.

Cancer metabolism : a therapeutic perspective (2016)
Journal Article
Martinez-Outschoorn, U., Peiris-Pagés, M., Pestell, R., Sotgia, F., & Lisanti, M. (2016). Cancer metabolism : a therapeutic perspective. Nature Reviews Clinical Oncology, 14, 11-31. https://doi.org/10.1038/nrclinonc.2016.60

Awareness that the metabolic phenotype of cells within tumours is heterogeneous — and distinct from that of their normal counterparts — is growing. In general, tumour cells metabolize glucose, lactate, pyruvate, hydroxybutyrate, acetate, glutamine, a... Read More about Cancer metabolism : a therapeutic perspective.

Repurposing atovaquone : targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells (2016)
Journal Article
Fiorillo, M., Lamb, R., Tanowitz, H., Mutti, L., Krstic- Demonacos, M., Cappello, A., …Lisanti, M. (2016). Repurposing atovaquone : targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells. Oncotarget, 7(23), 34084-34099. https://doi.org/10.18632/oncotarget.9122

Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis in immune-compromised patients. Atovaquone... Read More about Repurposing atovaquone : targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells.

Proteomic identification of prognostic tumour biomarkers, using chemotherapy-induced cancer-associated fibroblasts (2015)
Journal Article
Peiris-Pagès, M., Smith, D., Győrffy, B., Sotgia, F., & Lisanti, M. (2015). Proteomic identification of prognostic tumour biomarkers, using chemotherapy-induced cancer-associated fibroblasts. Aging, 7(10), 816-838. https://doi.org/10.18632/aging.100808

Cancer cells grow in highly complex stromal microenvironments, which through metabolic remodelling, catabolism, autophagy and inflammation nurture them and are able to facilitate metastasis and resistance to therapy. However, these changes in the met... Read More about Proteomic identification of prognostic tumour biomarkers, using chemotherapy-induced cancer-associated fibroblasts.

High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant (2015)
Journal Article
Farnie, G., Sotgia, F., & Lisanti, M. (2015). High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant. Oncotarget, 6(31), 30472-30486. https://doi.org/10.18632/oncotarget.5401

Chemo-resistance is a clinical barrier to more effective anti-cancer therapy. In this context, cancer stem-like cells (CSCs) are thought to be chemo-resistant, resulting in tumor recurrence and distant metastasis. Our hypothesis is that chemo-resista... Read More about High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant.

Mitochondrial mass, a new metabolic biomarker for stem-like cancer cells : understanding WNT/FGF-driven anabolic signaling (2015)
Journal Article
Lamb, R., Bonuccelli, G., Ozsvári, B., Peiris-Pagès, M., Fiorillo, M., Smith DL, D., …Lisanti, M. (2015). Mitochondrial mass, a new metabolic biomarker for stem-like cancer cells : understanding WNT/FGF-driven anabolic signaling. Oncotarget, 6(31), 30453-30471. https://doi.org/10.18632/oncotarget.5852

Here, we developed an isogenic cell model of “stemness” to facilitate protein biomarker discovery in breast cancer. For this purpose, we used knowledge gained previously from the study of the mouse mammary tumor virus (MMTV). MMTV initiates mammary t... Read More about Mitochondrial mass, a new metabolic biomarker for stem-like cancer cells : understanding WNT/FGF-driven anabolic signaling.

Dissecting tumor metabolic heterogeneity : Telomerase and large cell size metabolically define a sub-population of stem-like, mitochondrial-rich, cancer cells (2015)
Journal Article
Lamb, R., Ozsvari, B., Bonuccelli, G., Smith, D., Pestell, R., Martinez-Outschoorn, U., …Lisanti, M. (2015). Dissecting tumor metabolic heterogeneity : Telomerase and large cell size metabolically define a sub-population of stem-like, mitochondrial-rich, cancer cells. Oncotarget, 6(26), 21892-21905. https://doi.org/10.18632/oncotarget.5260

Tumor cell metabolic heterogeneity is thought to contribute to tumor recurrence, distant metastasis and chemo-resistance in cancer patients, driving poor clinical outcome. To better understand tumor metabolic heterogeneity, here we used the MCF7 brea... Read More about Dissecting tumor metabolic heterogeneity : Telomerase and large cell size metabolically define a sub-population of stem-like, mitochondrial-rich, cancer cells.

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