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One or more keywords matched the following properties of Macleod, Kay
PropertyValue
keywords Tumor metabolism
overview Understanding the role of mitochondria in tissue homeostasis and cancer. The Macleod Lab investigates how control of mitochondrial mass, mitochondrial function and mitochondrial signaling affects cellular responses to stress, homeostatic control of tissue maintenance and influences tumor growth and progression to malignancy. We use cutting edge approaches in cell and molecular biology, systems biology, novel mouse models and human patient samples to ask some of the most important questions about how mitochondria control tissue homeostasis, and how mitochondrial dysfunction contributes to cancer progression and metastasis. For example, we examine how BNIP3-dependent mitophagy is essential for proper metabolic zonation in the liver across the hypoxic gradient making up the liver lobule and how loss of BNIP3 promotes hepatic steatosis and liver cancer. This tumor suppressive role of BNIP3 involves coordinated turnover of lipid droplets with mitochondria at the autolysosome in a process we have termed “mitolipophagy”. In addition, we address how the BNIP3-related protein, BNIP3L (or NIX) which is also a mitochondrial cargo receptor, shares mitophagy functions with BNIP3 but we are increasingly focused on the divergent properties of BNIP3 and NIX in cellular growth control, both in the liver and in the pancreas. Our work indicates that while BNIP3 and NIX share functions in mitophagy in various tissues, they also possess unique growth control properties that explain how BNIP3 functions to suppress tumor growth while NIX acts as a tumor promoter. Ongoing work is addressing these functions in hepatocellular carcinoma, pancreatic ductal adenocarcinoma and in muscle atrophy linked to cancer cachexia. In other areas, we are examining how defects in mitophagy can promote tumor responses to chemotherapy and radiotherapy. Finally, we are examining how mitochondrial stress affects other signaling pathways in the cell.
One or more keywords matched the following items that are connected to Macleod, Kay
Item TypeName
Concept Breast Neoplasms
Concept DNA, Neoplasm
Concept Mammary Neoplasms, Experimental
Concept Energy Metabolism
Concept Neoplasm Transplantation
Concept Pancreatic Neoplasms
Concept Ovarian Neoplasms
Concept Lung Neoplasms
Concept Prostatic Neoplasms
Concept Head and Neck Neoplasms
Concept Biomarkers, Tumor
Concept Drug Resistance, Neoplasm
Concept Tumor Cells, Cultured
Concept Genes, Tumor Suppressor
Concept Mouth Neoplasms
Concept Neoplasm Metastasis
Concept Neoplasms, Experimental
Concept Tumor Burden
Concept Tumor Escape
Concept Mammary Neoplasms, Animal
Concept Nerve Sheath Neoplasms
Concept Tumor Suppressor Proteins
Concept Tumor Microenvironment
Concept Cell Line, Tumor
Concept Lipid Metabolism
Concept Neoplasm Invasiveness
Concept Neoplasms
Concept Tumor Suppressor Protein p53
Academic Article Insights into cancer from transgenic mouse models.
Academic Article Cell-autonomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system.
Academic Article A novel form of pRb expressed during normal myelopoiesis and in tumour-associated macrophages.
Academic Article c-Jun NH2-terminal kinase activating kinase 1/mitogen-activated protein kinase kinase 4-mediated inhibition of SKOV3ip.1 ovarian cancer metastasis involves growth arrest and p21 up-regulation.
Academic Article New paradigms for the function of JNKK1/MKK4 in controlling growth of disseminated cancer cells.
Academic Article The Rb tumor suppressor in stress responses and hematopoietic homeostasis.
Academic Article New roles for the RB tumor suppressor protein.
Academic Article The Rb tumor suppressor is required for stress erythropoiesis.
Academic Article Elevated poly-(ADP-ribose)-polymerase activity sensitizes retinoblastoma-deficient cells to DNA damage-induced necrosis.
Academic Article The role of the RB tumour suppressor pathway in oxidative stress responses in the haematopoietic system.
Academic Article BNip3 regulates mitochondrial function and lipid metabolism in the liver.
Academic Article Autophagy: cellular and molecular mechanisms.
Academic Article Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors.
Academic Article The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer?
Academic Article p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage.
Academic Article MKK4 suppresses metastatic colonization by multiple highly metastatic prostate cancer cell lines through a transient impairment in cell cycle progression.
Academic Article Mammary cancer initiation and progression studied with magnetic resonance imaging.
Academic Article Tumour suppressor gene function in carcinoma-associated fibroblasts: from tumour cells via EMT and back again?
Academic Article p62/SQSTM1 accumulation in squamous cell carcinoma of head and neck predicts sensitivity to phosphatidylinositol 3-kinase pathway inhibitors.
Academic Article Correlation of In Vivo and Ex Vivo ADC and T2 of In Situ and Invasive Murine Mammary Cancers.
Academic Article Tumor suppressor functions of BNIP3 and mitophagy.
Academic Article Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis.
Academic Article Derepression of mouse beta-major-globin gene transcription during erythroid differentiation.
Academic Article Autophagy Promotes Focal Adhesion Disassembly and Cell Motility of Metastatic Tumor Cells through the Direct Interaction of Paxillin with LC3.
Academic Article Novel insights into how autophagy regulates tumor cell motility.
Academic Article In Brief: Mitophagy: mechanisms and role in human disease.
Academic Article Autophagy in cancer metastasis.
Academic Article Small molecules inhibit STAT3 activation, autophagy, and cancer cell anchorage-independent growth.
Academic Article Expanding perspectives on the significance of mitophagy in cancer.
Academic Article Dia1-dependent adhesions are required by epithelial tissues to initiate invasion.
Academic Article Functions of autophagy in the tumor microenvironment and cancer metastasis.
Academic Article mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.
Academic Article Autophagy, cancer stem cells and drug resistance.
Academic Article Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer.
Academic Article Autophagy and cancer cell metabolism.
Academic Article Somatic mitochondrial mutation discovery using ultra-deep sequencing of the mitochondrial genome reveals spatial tumor heterogeneity in head and neck squamous cell carcinoma.
Academic Article Mitophagy in tumorigenesis and metastasis.
Academic Article ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3.
Concept Triple Negative Breast Neoplasms
Grant Autophagy in Tumor Progression and Metastasis
Grant Functions of pRb in Stress Erythropoiesis
Grant (PQ5) Consequences of imbalanced mitophagy and mitochondrial biogenesis in cancer
Grant Functions of BNIP3 in Mammary Tumorigenesis
Academic Article Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis.
Grant BNIP3 and BNIP3L (NIX) in lipid homeostasis and growth control in the liver
Academic Article DISSECTING TUMOR TRANSCRIPTIONAL HETEROGENEITY FROM SINGLE-CELL RNA-SEQ DATA BY GENERALIZED BINARY COVARIANCE DECOMPOSITION.
Search Criteria
  • Tumor
  • metabolism