Progressive loss of shape-responsive metabolic controls in cells with increasingly transformed phenotype

Wittelsberger, Scott C.; Kleene, Kenneth C.; Penman, Sheldon

doi:10.1016/0092-8674(81)90111-2

Cited by 131 publications

(83 citation statements)

References 12 publications

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“…The requirement for substratum adhesion in order to divide usually becomes less stringent as cells become transformed (Wittelsberger et al, 1981;Tucker et al ., 1981) . Although the P19 cell line is derived from a tumor, it still shows a strong substrate dependence for growth in the presence of defined growth factors .…”

Section: Resultsmentioning

confidence: 99%

“…The mitotic frequency of some nontransformed cell lines is dependent upon their adhesion to a solid surface, a process termed anchorage dependence for growth (Stoker et al, 1968) . This apparent requirement for cell adhesion becomes less stringent as the cells become more transformed, and this loss of substratum dependence for growth has become a criterion for transformation (Wittelsberger et al ., 1981;Tucker et al ., 1981) .…”

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confidence: 99%

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Substratum-growth factor collaborations are required for the mitogenic activities of activin and FGF on embryonal carcinoma cells.

Schubert

Kimura

1991

The Journal of Cell Biology

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Substratum-growth factor collaborations are required for the mitogenic activities of activin and FGF on embryonal carcinoma cells.

Schubert

Kimura

1991

The Journal of Cell Biology

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“…For example, loss of cell growth dependence on cell shape and surface contact in anchorage-dependent cells is a hallmark of tumor cells in vivo and has been induced in vitro (23). However, methods for the examination of how the mechanical and chemical factors of the cytoskeleton and the nuclear matrix integrate into a higher-order system are just beginning to emerge.…”

Section: Discussionmentioning

confidence: 99%

Engineering gene expression and protein synthesis by modulation of nuclear shape

Thomas

Collier

Sfeir

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

443

326

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The current understanding of the relationships between cell shape, intracellular forces and signaling, nuclear shape and organization, and gene expression is in its infancy. Here we introduce a method for investigating gene-specific responses in individual cells with controlled nuclear shape and projected area. The shape of the nuclei of primary osteogenic cells were controlled on microfabricated substrata with regiospecific chemistry by confining attachment and spreading of isolated cells on adhesive islands. Gene expression and protein synthesis were altered by changing nuclear shape. Collagen I synthesis correlated directly with cell shape and nuclear shape index (NSI), where intermediate values of nuclear distension (6 < NSI < 8) promoted maximum synthesis. Osteocalcin mRNA, a bone-specific differentiation marker, was observed intracellularly by using reverse transcription in situ PCR at 4 days in cells constrained by the pattern and not detected in unconstrained cells of similar projected area, but different NSI. Our data supports the concept of gene expression and protein synthesis based on optimal distortion of the nucleus, possibly altering transcription factor affinity for DNA, transport to the nucleus, or nuclear matrix organization. The combination of microfabricated surfaces, reverse transcription in situ PCR, and NSI measurement is an excellent system to study how transcription factors, the nuclear matrix, and the cytoskeleton interact to control gene expression and may be useful for studying a wide variety of other cell shape͞gene expression relationships.patterning ͉ cell size ͉ osteocalcin ͉ reverse transcription-PCR ͉ photolithography C ell morphology has a profound effect on a range of cellular events, such as proliferation (1-3), differentiation (4-7), cytoskeletal organization (8), and presumably gene expression. Changes to the cytoskeleton lead to altered stress levels imparted on the nucleus (9-11) and could affect organelle and DNA organization and distribution, ultimately altering cell function. For example, the rate of albumin secretion from hepatocytes can be altered by constraining cell size on patterned culture surfaces (3). In human epidermal kareatinocytes cell shape can modulate between terminal differentiation and proliferation (4). Furthermore, cells can be forced to enter the apoptotic cascade when the area on which the cell is allowed to spread is constrained (1). One proposed mechanism for the transduction of cell shape information into gene expression is through mechanical forces transmitted by means of the direct link of the cytoskeleton to the nucleus (9, 12), and in particular to nuclear matrix proteins (NMPs) such as NMP-1 and NMP-2 (13). These architectural transcription factors, which are components of the nuclear scaffold, induce changes in DNA supercoiling and can interact directly with gene promoter sequences (14). This interaction between the nuclear architecture and regulation of transcription or DNA topography raises the question of whether gross deformation of th...

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“…However, when placed on a rigid substrate on which they can exert strong forces, cells will flatten and proliferate. Many cancer cells appear to overcome this geometrical barrier and are able to proliferate even when placed in growth conditions that limit ECM and cell-cell interactions (so-called anchorage independent growth), suggesting that the cells have established a compensatory mechanism(s) [2]. However, in vivo, many tumors will modify their microenvironments to create a more rigid scaffold to stimulate proliferation [3,4].…”

Section: Introductionmentioning

confidence: 99%

Focal adhesion kinase as a regulator of cell tension in the progression of cancer

Tilghman¹,

Parsons²

2008

Seminars in Cancer Biology

142

115

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Growing evidence indicates that critical steps in cancer progression such as cell adhesion, migration, and cell cycle progression are regulated by the composition and organization of the microenvironment. The adhesion of cancer cells to components of the microenvironment and the forces transmitted to the cells via the actinomyosin network and the signaling complexes organized within focal adhesions allow cancer cells to sense the local topography of the extracellular matrix and respond efficiently to proximal growth and migration promoting cues. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is over expressed in a variety of cancers and plays an important role in cell adhesion, migration, and anchorage-dependent growth. In this review, we summarize evidence which implicate FAK in the ability of cells to sense and respond to local forces from the microenvironment through the regulation of adhesion dynamics and actinomyosin contractility, and we discuss the potential roles of FAK as a mechanosensor in the progression of cancer.

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Progressive loss of shape-responsive metabolic controls in cells with increasingly transformed phenotype

Cited by 131 publications

References 12 publications

Substratum-growth factor collaborations are required for the mitogenic activities of activin and FGF on embryonal carcinoma cells.

Substratum-growth factor collaborations are required for the mitogenic activities of activin and FGF on embryonal carcinoma cells.

Engineering gene expression and protein synthesis by modulation of nuclear shape

Focal adhesion kinase as a regulator of cell tension in the progression of cancer

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