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Cancer Cell Biology Research

Cancerous metastasis medical illustration.

Credit: iStock

Research in cancer cell biology seeks to define the biological basis for the differences between normal cells and cancer cells and to elucidate basic mechanisms that drive the development and behavior of tumors. Mechanistic understanding of this biology and these fundamental processes is critical for identifying molecular targets for therapeutic or preventive intervention.

Research in this area is supported and directed by the Cancer Cell Biology Branch (CCBB).

Cancer Cell Metabolism

Research in cancer cell metabolism focuses on altered cellular metabolism that supports the cancer phenotype characterized by unchecked cellular proliferation, resistance to metabolic and oxidative stress, ability to evade programmed cell death, reduced dependence on growth factor signals, insensitivity to growth inhibitory signals, and resistance to therapeutic intervention.

Key research areas include:

  • Oncogenic reprogramming of anaplerotic metabolism
  • Altered metabolic fuel homeostasis (e.g., the Warburg Effect, glutamine addiction, upregulated fatty acid metabolism)
  • The links between protein translation, ribosome biogenesis, and cellular metabolism
  • Tumor metabolite profiling and characterization
  • Regulation and mechanisms of nutrient, metabolic intermediate, and ion transport in cancer cells

Emerging areas relevant to this research include understanding the molecular link between body homeostasis and cancer cell biology, including obesity, the role of circadian rhythm in cancer biology, and molecular mechanisms that lead to cancer cachexia.

Cancer Cell Stress Responses

Cancer cell response to cellular and environmental stresses determines whether and how a cell dies or adapts to the stress in order to survive. Examples of types of stress included in this research are oxidative stress, oncogenic stress, accumulation of unfolded or misfolded proteins, hypoxia, metal-ion accumulation, chemotherapy, and inflammation.

Key research areas include:

  • Mechanisms of cell death (e.g., apoptosis, necrosis/necroptosis, autophagic cell death, anoikis, and other forms of programmed or non-programmed cell death)
  • Mechanisms the cell uses to control toxic byproducts of chemical reactions (e.g., redox control)
  • Recycling of cellular components (e.g., autophagy, mitophagy, lipophagy)
  • ER stress and the unfolded protein response
  • Stress-induced senescence
  • Macropinocytosis
  • Altered processing of growth factors and their associated receptors

Organelle Biology

Research funded in the area of organelle biology investigates the dysregulation of organelle biology in driving or supporting the cancer phenotype.

Key research areas include:

  • Dysregulated organelle biogenesis and function (e.g., mitochondria, endoplasmic reticulum, Golgi, lysosomes, lipid droplets, peroxisomes, endosomes, cilia)
  • Processing and trafficking of intracellular membranes and proteins
  • Endocytosis and endosome sorting and recycling
  • Interaction between nuclear-encoded oncogenic proteins and mitochondrial function
  • Organelle-specific differences between cancer stem cells and their differentiated progeny
  • Role of cancer cell organelles in cancer-associated phenotypes

Emerging areas relevant to this research include inter-organelle communication among the nucleus, mitochondria, and endoplasmic reticulum. Studies that connect organelle structure and morphology to the phenotypic state or function of cancer cells are of high interest.

Cancer Cell Cycle Control

Cell cycle dysregulation is a hallmark of cancer, and cell cycle components have been aggressively targeted in chemotherapeutic strategies. Research in this area focuses on altered cell cycle regulation and its contribution to oncogenic transformation and tumor maintenance.

Key research areas include:

  • Characterization of factors that regulate the cell cycle, mitosis, cytokinesis, centrosome duplication, and DNA replication in cancer cells and tumor tissues
  • Alternative, kinase-independent functions of core cell cycle regulators
  • Mechanisms that alter protein stability and function in cancer cells, including proteasome-mediated degradation and protein modifications by ubiquitylation, sumoylation, and neddylation

Emerging areas relevant to this research include senescence as an oncogenic mechanism through the senescence-associated secretory phenotype; the relationship between quiescence, senescence, and dormancy in cancer cells; and the elucidation of nutrient-sensing cell cycle checkpoints.

Post-transcriptional Gene Regulation and Cancer

Stresses such as misfolded proteins, hypoxia, chemotherapy, and others cause genetic mutations, but the mutations have a functional effect only when they are transcribed into RNA. Research on post-transcriptional gene regulation and cancer investigates mechanisms influencing the cancer phenotype.

Key research areas include:

  • Altered mechanisms affecting RNA stability, splicing, transport, and mRNA translation
  • Regulation and mechanism of alternative splicing in cancer
  • The role of non-coding RNAs and RNA binding proteins in the regulation of splicing, translation, and mRNA stability
  • Translation factors such as oncogenes and tumor suppressors
  • Changes in protein maturation, stability, and post-translational modifications as drivers for tumorigenesis or cancer progression

Emerging areas relevant to this research include the study of chemical modifications to RNA and RNA binding proteins that affect RNA stability, splicing, transport, and mRNA translation and the role of aberrant ribosomal biogenesis in cancer.

Basic Mechanisms of Cellular Transformation

Research on the basic mechanisms by which normal cells become cancerous and the identification of cells of origin for solid tumors is essential to better understand, diagnose, and treat cancer.

Key research areas include:

  • Functional and molecular characterization of oncogenes and tumor suppressors
  • Oncogenic signal transduction - network and component analyses and rewiring
  • Signaling stimulated by growth factors and their receptors
  • The role of cytokines and associated inflammatory signaling cascades in oncogenic transformation
  • Mechanisms associated with the regulation of cell fate decisions
  • The biology of tumor-initiating cells and cancer stem cells
  • Mechanisms of cellular immortalization as a prerequisite for oncogenic transformation
  • Role of developmental genes and cellular differentiation in cancer
  • Relationship between cellular senescence, cellular aging, and cancer

Emerging areas relevant to this research include the biology of preneoplastic lesions, cell competition, and the cancer field effect.

Biospecimen Resources to Support Studies in Cancer Biology

DCB supports the development of a number of resources that collect, store, process, and disseminate human biological specimens—including nucleic acids and tissue arrays—and associated data for studies of human cancer biology, particularly early events in oncogenic transformation.

Specific resources supported include:

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