Elucidate growth control mechanisms using reconstructed spatiotemporal distributions of signaling events

The cells populating the intestinal crypts are part of a dynamic tissue system which involves the self–renewal of stem cells, a commitment to proliferation, lineage–specific differentiation, movement and cell death. Our knowledge of these processes is limited, but even now there are important clues to the nature of the regulatory systems, and these clues are leading to a better understanding of intestinal cancers. Few intestinal–specific markers have been described; however, homeobox genes such as cdx–2 appear to be important for morphogenic events in the intestine. There are several intestinal cell surface proteins such as the A33 antigen which have been used as targets for immunotherapy. Many regulatory cytokines (lymphokines or growth factors) influence intestinal development: enteroglucagon, IL–2, FGF, EGF family members. In conjunction with cell–cell contact and/or ECM, these cytokines lead to specific differentiation signals. Although the tissue distribution of mitogens such as EGF, TGFα, amphiregulin, betacellulin, HB–EGF and cripto have been studied in detail, the physiological roles of these proteins have been difficult to determine. Clearly, these mitogens and the corresponding receptors are involved in the maintenance and progression of the tumorigenic state. The interactions between mitogenic, tumour suppressor and oncogenic systems are complex, but the tumorigenic effects of multiple lesions in intestinal carcinomas involve synergistic actions from lesions in these different systems. Together, the truncation of apc and activation of the ras oncogene are sufficient to induce colon tumorigenesis. If we are to improve cancer therapy, it is imperative that we discover the biological significance of these interactions, in particular the effects on cell division, movement and survival.

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Genomic-stability and growth-control mechanisms involving the p38 MAP kinase signaling pathway - identification of potential targets for cancer therapy

European Journal of Cancer ◽

10.1016/s0959-8049(02)81041-3 ◽

2002 ◽

Vol 38 ◽

pp. S117

Keyword(s):

Cancer Therapy ◽

Map Kinase ◽

Signaling Pathway ◽

Growth Control ◽

Genomic Stability ◽

P38 Map Kinase ◽

Control Mechanisms ◽

Kinase Signaling ◽

Kinase Signaling Pathway ◽

Map Kinase Signaling Pathway

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Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data

PLoS Computational Biology ◽

10.1371/journal.pcbi.1004412 ◽

2016 ◽

Vol 12 (2) ◽

pp. e1004412 ◽

Cited By ~ 42

Author(s):

Nick Jagiella ◽

Benedikt Müller ◽

Margareta Müller ◽

Irene E. Vignon-Clementel ◽

Dirk Drasdo

Keyword(s):

Growth Control ◽

Image Data ◽

Control Mechanisms ◽

Cellular Spheroids

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Studies of Biochemistry and Physiology of Normal and Tumour Strain Cells: Growth Control Mechanisms in Normal and Tumour Strain Cells

Nature ◽

10.1038/198153a0 ◽

1963 ◽

Vol 198 (4876) ◽

pp. 153-153 ◽

Cited By ~ 3

Keyword(s):

Growth Control ◽

Control Mechanisms

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Growth control mechanisms in neuronal regeneration

FEBS Letters ◽

10.1016/j.febslet.2015.04.046 ◽

2015 ◽

Vol 589 (14) ◽

pp. 1669-1677 ◽

Cited By ~ 28

Author(s):

Ella Doron-Mandel ◽

Mike Fainzilber ◽

Marco Terenzio

Keyword(s):

Growth Control ◽

Control Mechanisms ◽

Neuronal Regeneration

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Interplay between cell proliferation and recruitment controls the duration of growth and final size of the Drosophila wing

10.1101/2021.05.14.444212 ◽

2021 ◽

Author(s):

Elizabeth Diaz-Torres ◽

Luis Manuel Muñoz-Nava ◽

Marcos Nahmad

Keyword(s):

Cell Proliferation ◽

Growth Control ◽

Control Mechanisms ◽

Final Size ◽

Exponential Process ◽

Drosophila Cell ◽

Cell Recruitment ◽

Drosophila Wing ◽

Long Time ◽

Cell Growth And Proliferation

How organs robustly attain a final size despite perturbations in cell growth and proliferation rates is a fundamental question in developmental biology. Since organ growth is an exponential process driven mainly by cell proliferation, even small variations in cell proliferation rates, when integrated over a relatively long time, will lead to large differences in size, unless intrinsic control mechanisms compensate for these variations. Here we use a mathematical model to consider the hypothesis that in the developing wing of Drosophila, cell recruitment, a process in which undifferentiated neighboring cells are incorporated into the wing primordium, determines the time in which growth is arrested in this system. Under this assumption, our model shows that perturbations in proliferation rates of wing-committed cells are compensated by an inversely proportional duration of growth. This mechanism ensures that the final size of the wing is robust in a range of cell proliferation rates. Furthermore, we predict that growth control is lost when fluctuations in cell proliferation affects both wing-committed and recruitable cells. Our model suggests that cell recruitment may act as a temporal controller of growth to buffer fluctuations in cell proliferation rates, offering a solution to a long-standing problem in the field.

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