ERR{alpha} Maintains Mitochondrial Oxidative Metabolism and Constitutes an Actionable Target in PGC1{alpha}-Elevated Melanomas

The uncontrolled growth of tumors provides metabolic dependencies that can be harnessed for therapeutic benefit. Although tumor cells exhibit these increased metabolic demands due to their rapid proliferation, these metabolic processes are general to all cells, and furthermore, targeted therapeutic intervention can provoke compensatory adaptation that alters tumors' characteristics. As an example, a subset of melanomas depends on the transcriptional coactivator PGC1α function to sustain their mitochondrial energy-dependent survival. However, selective outgrowth of resistant PGC1α-independent tumor cells becomes endowed with an augmented metastatic phenotype. To find PGC1α-dependent components that would not affect metastasis in melanomas, an unbiased proteomic analyses was performed and uncovered the orphan nuclear receptor ERRα, which supports PGC1α's control of mitochondrial energetic metabolism, but does not affect the antioxidant nor antimetastatic regulatory roles. Specifically, genetic or pharmacologic inhibition of ERRα reduces the inherent bioenergetic capacity and decreases melanoma cell growth, but without altering the invasive characteristics. Thus, within this particularly aggressive subset of melanomas, which is characterized by heighted expression of PGC1α, ERRα specifically mediates prosurvival functions and represents a tangible therapeutic target. Implications: ERRα, a druggable protein, mediates the bioen...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Metabolism Source Type: research

Related Links:

by Dante Garcia, MD; Itisha S. Jefferson, BS; Pablo Ramirez, BS; Angelina Palomino, BS; William Adams, PhD; Jessica Vera, BSN; Ruby De La Torre, APN; Kristin Lee, MD; Ashley Elsensohn, MD, MPH; Hana Kazbour, MD; and Rebecca Tung, MD Dr. Garcia is with the Department of Internal Medicine at Loma Linda University in Loma Linda, […]
Source: Journal of Clinical and Aesthetic Dermatology - Category: Dermatology Authors: Tags: Basal Cell Carcinoma Cutaneous Oncology Medical Issues Melanoma Original Research Patient Education Photoaging Squamous Cell Carcinoma Sunburn and Sun Care Videos Skin Cancer Source Type: research
Publication date: Available online 27 January 2020Source: Inorganic Chemistry CommunicationsAuthor(s): Camila F.N. da Silva, Loyanne Carla Barbosa Ramos, Thomas N. Rohrabaugh, Jessica Vandervord, Roberto Santana da Silva, Claudia Turro, Sofia NikolaouAbstractThis work evaluates the cytotoxicity of [Ru3(μ3-O)(μ-OAc)5{μ-η1(C),η2(N,N)-phen}(py)2](PF6) (1), a triruthenium acetate cluster combined with an ortho-metallated 1,10-phenanthroline (phen) ligand, along with its interactions with biomolecules. In vitro cytotoxicity tests against the B16F10 (murine melanoma) and L929 (fibroblast) cell lines showed that ...
Source: Inorganic Chemistry Communications - Category: Chemistry Source Type: research
ONCOS-102, a promising immunotherapy vaccine, is moving closer to becoming a part of future first-line treatment for mesothelioma. Early clinical trial results announced this week show safety and efficacy when the vaccine is used in combination with standard-of-care chemotherapy for patients with inoperable pleural mesothelioma. Targovax, a Scandinavian pharmaceutical company developing the drug, is moving forward with another study combining ONCOS-102 with a checkpoint inhibitor drug such as Keytruda (pembrolizumab) or Opdivo (nivolumab), along with chemotherapy. “We have seen enough data at this point to be going ...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
(Estonian Research Council) Worldwide, the incidence rates of skin cancer, like other types of cancer, is increasing. People in Europe and the Nordic countries are, compared to other areas of the world, at a higher risk of developing skin cancer due to their predominantly light and sun-sensitive skin type. The number of new cases of cancer in Estonia and Nordic countries has reached the same level as in sunny Australia, New Zealand and Florida.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Contributors : Daniel Baumann ; Rienk OffringaSeries Type : Expression profiling by arrayOrganism : Mus musculusCancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression of immune cell function by cytostatic drugs may limit therapeutic efficacy. Here we show that targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) does not impair dendritic cell-mediated T-cell p...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research
AbstractA new series of tetrahydroquinoline-isoxazoline hybrid derivatives (3a –p) were efficiently synthesized involving 1,3-dipolar cycloaddition reaction according to click chemistry approach, from the corresponding N-allyl-4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines preformed, with moderate to good yields (63 –77%). To establish new candidates with anticancer activity, the antiproliferative effect of these compounds was measured by the MTT assay on different cancer cell lines such as human breast adenocarcinoma (MCF-7), human liver carcinoma (HepG2), human lung adenocarcinoma (A549), cervical cancer (H eLa...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research
Abstract Chemokines and their receptors have been reported to drive immune cells into tumours or to be directly involved in the promotion or inhibition of the development of tumours. However, their expression in regional lymph node (LN) tissues in melanoma patients remains unknown. The present study investigated the relationship between the expression of mRNA of chemokines and their receptors and clinicopathology of the regional LN tissues of skin cutaneous melanoma (SKCM) patients available in The Cancer Genome Atlas. The relationship between chemokines and their receptors and the composition of immune cells with...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Conclusions: CT-based surface mould brachytherapy results in better conformity of superficial lesions on small, irregular surfaces such as the nose and inner canthus than electrons with a slightly higher skin dose. PMID: 31969913 [PubMed]
Source: Journal of Contemporary Brachytherapy - Category: Cancer & Oncology Tags: J Contemp Brachytherapy Source Type: research
Over the past several years, a wave of new cancer immunotherapy agents referred to as immune checkpoint inhibitors (ICIs) have transformed the standard of care for patients with cancer. ICIs are most commonly used in advanced cancers with palliative intent and recently as frontline therapy for some cancers. These new agents have been shown to extend overall survival (OS) and progression free survival (PFS) in patients with lung cancer, melanoma, Hodgkin lymphoma, renal cell carcinoma, urothelial carcinoma, Merkel cell carcinoma, head and neck cancer, and more.
Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: Source Type: research
Conclusion: Albeit limited in scope, our data suggest that cytotoxic therapy with nab-paclitaxel and bevacizumab appear to favorably alter systemic parameters of immune function of potential benefit in combination T-cell directed immune checkpoint inhibitor therapy.
Source: American Journal of Clinical Oncology - Category: Cancer & Oncology Tags: Original Articles: Cutaneous Source Type: research
More News: Antidoxidants | Cancer | Cancer & Oncology | Genetics | Melanoma | Skin Cancer