title: NF-κB signalling and cell fate decisions in response to a short pulse of tumour necrosis factor.
abstract: In tissues and tumours, cell behaviours are regulated by multiple time-varying signals. While in the laboratory cells are often exposed to a stimulus for the duration of the experiment, in vivo exposures may be much shorter. In this study, we monitored NF-κB and caspase signalling in human cancer cells treated with a short pulse of Tumour Necrosis Factor (TNF). TNF is an inflammatory cytokine that can induce both the pro-survival NF-κB-driven gene transcription pathway and the pro-apoptotic caspase pathway. We find that a few seconds of exposure to TNF is sufficient to activate the NF-κB pathway in HeLa cells and induce apoptotic cell death in both HeLa and Kym-1 cells. Strikingly, a 1-min pulse of TNF can be more effective at killing than a 1-hour pulse, indicating that in addition to TNF concentration, duration of exposure also coordinates cell fate decisions.
authors.affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robin E C
authors.initials: RE
authors.lastname: Lee
authors.affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.|Biomedical Engineering Department, McGill University, Montréal, Québec, H3A 2B4 Canada.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Qasaimeh
authors.affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Xia
authors.affiliation: Biomedical Engineering Department, McGill University, Montréal, Québec, H3A 2B4 Canada.|McGill University and Genome Québec Innovation Centre, Montréal, Québec, H3A 0G1, Canada.|Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, H3A 2B4 Canada.
authors.forename: David
authors.initials: D
authors.lastname: Juncker
authors.affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gaudet
mesh_terms: D021581:Active Transport, Cell Nucleus; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D019070:Cell Lineage; D016207:Cytokines / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation; D044085:Microfluidics; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases