Molecular theory of cancer

Blagosklonny, Mikhail V.

doi:10.4161/cbt.4.6.1818

Cited by 56 publications

(40 citation statements)

References 112 publications

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“…This fact alone evidently suggests that the network properties can be affected both genetically, such as mutations, and epidemiologically, such as by other tissues. Therefore, the postulation of such endogenous network to understand cancer immediately provides a possible platform to understand the dichotomy between whether cancer is a genetic disease [25][26][27][28][29] or an epigenetic disease [30][31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Ao¹,

Galas²,

Hood³

et al. 2008

Medical Hypotheses

145

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SummaryAn endogenous molecular-cellular network for both normal and abnormal functions is assumed to exist. This endogenous network forms a nonlinear stochastic dynamical system, with many stable attractors in its functional landscape. Normal or abnormal robust states can be decided by this network in a manner similar to the neural network. In this context cancer is hypothesized as one of its robust intrinsic states.This hypothesis implies that a nonlinear stochastic mathematical cancer model is constructible based on available experimental data and its quantitative prediction is directly testable. Within such model the genesis and progression of cancer may be viewed as stochastic transitions between different attractors. Thus it further suggests that progressions are not arbitrary. Other important issues on cancer, such as genetic vs epigenetics, double-edge effect, dormancy, are discussed in the light of present hypothesis. A different set of strategies for cancer prevention, cure, and care, is therefore suggested.

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Section: Discussionmentioning

confidence: 99%

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Ao¹,

Galas²,

Hood³

et al. 2008

Medical Hypotheses

145

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“…99 However, this concept is still contentious. 133 Considering the potential increased mutation rate in inflamed microenvironment, it is possible that the resident stromal cells could accumulate a random set of mutations. On the other hand, the classical working hypotheses on carcinogenesis assumes the mutation rate is affected by overall rate of proliferation, early in premalignant conditions 79 lead to an intrinsic increase in mutation rate, as well as loss of mechanisms that monitor genomic integrity and control the appropriate cellular response, such as DNA repair or cell death.…”

Section: The Mutational Model Of Cafsmentioning

confidence: 99%

Origin of carcinoma associated fibroblasts

Haviv¹,

Polyák²,

Qiu³

et al. 2009

Cell Cycle

105

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“…In some instances, the alternate states adopted by the cells are so stable that they can be transmitted through cell divisions, as exemplified by the crippled growth (CG) degeneration of the filamentous fungus Podospora anserina (reviewed in Lalucque et al 2010). This kind of regulatory inheritance is now suspected of playing an important role in various physiological processes, including tumor formation, cell differentiation, and degeneration (Blagosklonny 2005;Lalucque et al 2010), yet it is still poorly studied.…”

mentioning

confidence: 99%

A Non-Mendelian MAPK-Generated Hereditary Unit Controlled by a Second MAPK Pathway inPodospora anserina

et al. 2012

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The Podospora anserina PaMpk1 MAP kinase (MAPK) signaling pathway can generate a cytoplasmic and infectious element resembling prions. When present in the cells, this C element causes the crippled growth (CG) cell degeneration. CG results from the inappropriate autocatalytic activation of the PaMpk1 MAPK pathway during growth, whereas this cascade normally signals stationary phase. Little is known about the control of such prion-like hereditary units involved in regulatory inheritance. Here, we show that another MAPK pathway, PaMpk2, is crucial at every stage of the fungus life cycle, in particular those controlled by PaMpk1 during stationary phase, which includes the generation of C. Inactivation of the third P. anserina MAPK pathway, PaMpk3, has no effect on the development of the fungus. Mutants of MAPK, MAPK kinase, and MAPK kinase kinase of the PaMpk2 pathway are unable to present CG. This inability likely relies upon an incorrect activation of PaMpk1, although this MAPK is normally phosphorylated in the mutants. In PaMpk2 null mutants, hyphae are abnormal and PaMpk1 is mislocalized. Correspondingly, stationary phase differentiations controlled by PaMpk1 are defective in the mutants of the PaMpk2 cascade. Constitutive activation of the PaMpk2 pathway mimics in many ways its inactivation, including an effect on PaMpk1 localization. Analysis of double and triple mutants inactivated for two or all three MAPK genes undercover new growth and differentiation phenotypes, suggesting overlapping roles. Our data underscore the complex regulation of a prion-like element in a model organism.

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Molecular theory of cancer

Cited by 56 publications

References 112 publications

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Origin of carcinoma associated fibroblasts

A Non-Mendelian MAPK-Generated Hereditary Unit Controlled by a Second MAPK Pathway inPodospora anserina

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