Cell growth

About: Cell growth is a research topic. Over the lifetime, 104237 publications have been published within this topic receiving 3751303 citations. The topic is also known as: GO:0016049 & cellular growth.

Inhibition of Metastatic Outgrowth from Single Dormant Tumor Cells by Targeting the Cytoskeleton

Abstract: Metastatic breast cancer may emerge from latent tumor cells that remain dormant at disseminated sites for many years. Identifying mechanisms regulating the switch from dormancy to proliferative metastatic growth has been elusive due to the lack of experimental models of tumor cell dormancy. We characterized the in vitro growth characteristics of cells that exhibit either dormant (D2.0R, MCF-7, and K7M2AS1.46) or proliferative (D2A1, MDA-MB-231, and K7M2) metastatic behavior in vivo. Although these cells proliferate readily in two-dimensional culture, we show that when grown in three-dimensional matrix, distinct growth properties of the cells were revealed that correlate to their dormant or proliferative behavior at metastatic sites in vivo. In three-dimensional culture, cells with dormant behavior in vivo remained cell cycle arrested with elevated nuclear expression of p16 and p27. The transition from quiescence to proliferation of D2A1 cells was dependent on fibronectin production and signaling through integrin beta1, leading to cytoskeletal reorganization with filamentous actin (F-actin) stress fiber formation. We show that phosphorylation of myosin light chain (MLC) by MLC kinase (MLCK) through integrin beta1 is required for actin stress fiber formation and proliferative growth. Inhibition of integrin beta1 or MLCK prevents transition from a quiescent to proliferative state in vitro. Inhibition of MLCK significantly reduces metastatic outgrowth in vivo. These studies show that the switch from dormancy to metastatic growth may be regulated, in part, through epigenetic signaling from the microenvironment, leading to changes in the cytoskeletal architecture of dormant cells. Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch.

Functional Role of Glycosphingolipids in Cell Recognition and Signaling

Abstract: Glycosphingolipids (GSLs), cell type-specific markers which change dramatically during ontogenesis and oncogenesis, have been implicated as playing major roles in cellular interactions and control of cell proliferation in multicellular organisms. These functional roles have been partially clarified through two types of studies: (i) Studies of cell recognition mediated by (a) GSL-GSL interaction, (b) GSL-lectin interaction, and (c) GSL-dependent modulation of integrin receptor function. (ii) Studies on control of transmembrane signaling by GSLs and/or sphingosine (Sph) derivatives, with emphasis on effects of these compounds on: (a) signaling pathways initiated by tyrosine kinase-linked receptors; (b) signaling systems mediated by protein kinase C, MAP kinase, other kinases, or cytosolic Ca2+ concentration, leading to changes in cellular phenotypes such as motility, proliferation, differentiation, and apoptosis.

The role of c-myc in cellular growth control.

Abstract: Cell division is coupled to cell growth. Since some c-myc target genes are regulators of cell growth while others function in cell division pathways, c-myc is apparently poised at the interface of these processes. Cell culture systems have shown specific myc-associated growth phenotypes. Increased cell growth precedes DNA synthesis after myc activation in cells expressing myc-estrogen receptor fuson constructs and cells lacking c-myc exhibit a marked loss of protein synthesis. A number of candidate c-myc target genes regulate processes required for cell growth including rRNA transcription and processing, ribosomal protein transcription and translation, and translation initiation. These interactions all have the potential to account for the growth phenotypes in c-myc mutant cells. The ability of translation initiation factors, including eIF4E, to transform cells makes them particularly interesting targets of c-myc. Further evaluation of these target genes will provide important insights into growth control and c-myc's functions in cellular proliferation.