Open questions: The disrupted circuitry of the cancer cell
Abstract
Every new decade of biology brings with it a change in outlook driven by new technologies and fresh perspectives. Such is the case for cancer and how we consider the disease. The advent of molecular biology led to the identification of altered signaling molecules and 'oncogenes' that were proposed to drive uncontrolled cell proliferation. The rise of cell biology and new imaging and culturing technologies led to the idea that disruptions in the extracellular environment prime cells for transformation. In the current genomics era, cancer is most commonly seen as a genetic disorder where an unstable genome gives rise to a variety of different cell variants that are selected for proliferation and survival. All of these views are partially correct, of course, and are simply different ways of saying that genetic alterations in cancer cells result in a loss of growth homeostasis. They also take the view that molecular changes 'drive' a cell to grow uncontrollably, rather than tip the balance from one normal state (quiescence) to another (proliferation). Underlying this oversimplification is a profound ignorance of what controls homeostatic cell growth in the first place and how specific mutations impact it. Normal, proliferation-competent cells can accurately monitor their environmentmore »
- Authors:
-
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1208943
- Grant/Contract Number:
- AC05-76RL01830
- Resource Type:
- Accepted Manuscript
- Journal Name:
- BMC Biology
- Additional Journal Information:
- Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 1741-7007
- Publisher:
- BioMed Central
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Wiley, H. Steven. Open questions: The disrupted circuitry of the cancer cell. United States: N. p., 2014.
Web. doi:10.1186/s12915-014-0088-y.
Wiley, H. Steven. Open questions: The disrupted circuitry of the cancer cell. United States. https://doi.org/10.1186/s12915-014-0088-y
Wiley, H. Steven. Sat .
"Open questions: The disrupted circuitry of the cancer cell". United States. https://doi.org/10.1186/s12915-014-0088-y. https://www.osti.gov/servlets/purl/1208943.
@article{osti_1208943,
title = {Open questions: The disrupted circuitry of the cancer cell},
author = {Wiley, H. Steven},
abstractNote = {Every new decade of biology brings with it a change in outlook driven by new technologies and fresh perspectives. Such is the case for cancer and how we consider the disease. The advent of molecular biology led to the identification of altered signaling molecules and 'oncogenes' that were proposed to drive uncontrolled cell proliferation. The rise of cell biology and new imaging and culturing technologies led to the idea that disruptions in the extracellular environment prime cells for transformation. In the current genomics era, cancer is most commonly seen as a genetic disorder where an unstable genome gives rise to a variety of different cell variants that are selected for proliferation and survival. All of these views are partially correct, of course, and are simply different ways of saying that genetic alterations in cancer cells result in a loss of growth homeostasis. They also take the view that molecular changes 'drive' a cell to grow uncontrollably, rather than tip the balance from one normal state (quiescence) to another (proliferation). Underlying this oversimplification is a profound ignorance of what controls homeostatic cell growth in the first place and how specific mutations impact it. Normal, proliferation-competent cells can accurately monitor their environment and respond appropriately to perturbation, whether it is a loss of neighbors or an inflammatory stimulus. Cancer cells either proliferate or refuse to die where and when they should not, which clearly indicates that they have problems in detecting or responding to their environment. Thus, an enormous amount of effort has gone into defining the signaling pathways that can trigger a proliferative response and the biochemical mechanisms underlying these pathways. Far less work has focused on understanding the higher-order logic of these pathways and the roles played by all of the components as part of an integrated system. In other words, we do not really understand how cells process information and make decisions and thus cannot predict how any given molecular change will alter what a cell does.},
doi = {10.1186/s12915-014-0088-y},
journal = {BMC Biology},
number = 1,
volume = 12,
place = {United States},
year = {Sat Oct 18 00:00:00 EDT 2014},
month = {Sat Oct 18 00:00:00 EDT 2014}
}
Web of Science
Works referenced in this record:
Recurrent design patterns in the feedback regulation of the mammalian signalling network
journal, January 2008
- Legewie, Stefan; Herzel, Hanspeter; Westerhoff, Hans V.
- Molecular Systems Biology, Vol. 4, Issue 1
Genomic Sequencing for Cancer Diagnosis and Therapy
journal, January 2014
- Wang, Linghua; Wheeler, David A.
- Annual Review of Medicine, Vol. 65, Issue 1
The Mammalian MAPK/ERK Pathway Exhibits Properties of a Negative Feedback Amplifier
journal, December 2010
- Sturm, O. E.; Orton, R.; Grindlay, J.
- Science Signaling, Vol. 3, Issue 153
Macrophages: Obligate Partners for Tumor Cell Migration, Invasion, and Metastasis
journal, January 2006
- Condeelis, John; Pollard, Jeffrey W.
- Cell, Vol. 124, Issue 2
The Hallmarks of Cancer
journal, January 2000
- Hanahan, Douglas; Weinberg, Robert A.
- Cell, Vol. 100, Issue 1
Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling
journal, February 2013
- Huang, Shao-shan Carol; Clarke, David C.; Gosline, Sara J. C.
- PLoS Computational Biology, Vol. 9, Issue 2
IGF binding proteins in cancer: mechanistic and clinical insights
journal, April 2014
- Baxter, Robert C.
- Nature Reviews Cancer, Vol. 14, Issue 5
Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context
journal, January 2010
- Joslin, Elizabeth J.; Shankaran, Harish; Opresko, Lee K.
- Molecular BioSystems, Vol. 6, Issue 7
Feedback regulation of EGFR signalling: decision making by early and delayed loops
journal, January 2011
- Avraham, Roi; Yarden, Yosef
- Nature Reviews Molecular Cell Biology, Vol. 12, Issue 2
Putting tumours in context
journal, October 2001
- Bissell, Mina J.; Radisky, Derek
- Nature Reviews Cancer, Vol. 1, Issue 1
Computational modeling of the EGF-receptor system: a paradigm for systems biology
journal, January 2003
- Steven Wiley, H.
- Trends in Cell Biology, Vol. 13, Issue 1
Putting tumours in context
journal, October 2001
- Bissell, Mina J.; Radisky, Derek
- Nature Reviews Cancer, Vol. 1, Issue 1
Recurrent design patterns in the feedback regulation of the mammalian signalling network
journal, January 2008
- Legewie, Stefan; Herzel, Hanspeter; Westerhoff, Hans V.
- Molecular Systems Biology, Vol. 4, Issue 1
IGF binding proteins in cancer: mechanistic and clinical insights
journal, April 2014
- Baxter, Robert C.
- Nature Reviews Cancer, Vol. 14, Issue 5
Feedback regulation of EGFR signalling: decision making by early and delayed loops
journal, January 2011
- Avraham, Roi; Yarden, Yosef
- Nature Reviews Molecular Cell Biology, Vol. 12, Issue 2
Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context
journal, January 2010
- Joslin, Elizabeth J.; Shankaran, Harish; Opresko, Lee K.
- Molecular BioSystems, Vol. 6, Issue 7
The Mammalian MAPK/ERK Pathway Exhibits Properties of a Negative Feedback Amplifier
journal, December 2010
- Sturm, O. E.; Orton, R.; Grindlay, J.
- Science Signaling, Vol. 3, Issue 153
Genomic Sequencing for Cancer Diagnosis and Therapy
journal, January 2014
- Wang, Linghua; Wheeler, David A.
- Annual Review of Medicine, Vol. 65, Issue 1
Negative Feedback and Adaptive Resistance to the Targeted Therapy of Cancer
journal, March 2012
- Chandarlapaty, Sarat
- Cancer Discovery, Vol. 2, Issue 4
Works referencing / citing this record:
Cancer drug target identification and node-level analysis of the network of MAPK pathways
journal, March 2018
- Aksam, V. K. Md; Chandrasekaran, V. M.; Pandurangan, Sundaramurthy
- Network Modeling Analysis in Health Informatics and Bioinformatics, Vol. 7, Issue 1
Therapeutic control and resistance of the EGFR-driven signaling network in glioblastoma
journal, March 2015
- Azuaje, Francisco; Tiemann, Katja; Niclou, Simone P.
- Cell Communication and Signaling, Vol. 13, Issue 1