Retraction: Comparing gas transport in three polymers via molecular dynamics simulation.

Retraction of 'Comparing gas transport in three polymers via molecular dynamics simulation' by Luke R. Anderson et al., Phys. Chem. Chem. Phys., 2018, 20, 22123-22133, https://doi.org/10.1039/C8CP02829J.

Comparing gas transport in three polymers via molecular dynamics simulation.

People use polymers as materials for preparing separation media or containers. It is necessary to have a molecular level profound knowledge of gas transport in e bulk and interface regimes of different polymers, but few researchers have done a molecular level study of the bulk and interface behavior of gases in several types of non-homologen polymers thoroughly or developed expressions to correlate gas transport properties with cavity size distribution and chain oscillation flexibility. Therefore, in this work, molecular dynamics (MD) simulation was employed to study the transport of methane and n-butane molecules in the bulk and interface region of polyethylene (PE), poly(4-methyl-2-pentyne) (PMP) and polydimethylsiloxane (PDMS). Penetrant diffusivity, solubility and permeability in the bulk were studied first. The subdiffusion behavior of gas molecules is explored to obtain the mechanisms behind penetrant transport. Both penetrants have much smaller diffusivities in PE than in PMP and PDMS, and they have larger diffusivities in PDMS than in PMP. PE has lower accessible cavity fraction (ACF) and average oscillation amplitudes (AOAs) of the chains than PDMS and PMP. PE also has much smaller solubilities and permeabilities of both penetrants than PDMS and PMP. Though the permeabilities of both penetrants in PDMS are higher than the corresponding values in PMP, PMP has a higher selectivity of n-butane over methane than PDMS. Nonequilibrium MD simulation was performed to study the interface property and gas transport in the interface region. Equations to predict penetrant diffusivity and permeability from the accessible cavity fraction (ACF) and average amplitude of chain oscillation were developed successfully. Penetrant diffusivity and permeability are proportional to the value of ACF to the power of one third and that of ACF to the power of four thirds, respectively.

Structural and mechanical functions of integrins.

Integrins are ubiquitously expressed cell surface receptors that play a critical role in regulating the interaction between a cell and its microenvironment to control cell fate. These molecules are regulated either via their expression on the cell surface or through a unique bidirectional signalling mechanism. However, integrins are just the tip of the adhesome iceberg, initiating the assembly of a large range of adaptor and signalling proteins that mediate the structural and signalling functions of integrin. In this review, we summarise the structure of integrins and mechanisms by which integrin activation is controlled. The different adhesion structures formed by integrins are discussed, as well as the mechanical and structural roles integrins play during cell migration. As the function of integrin signalling can be quite varied based on cell type and context, an in depth understanding of these processes will aid our understanding of aberrant adhesion and migration, which is often associated with human pathologies such as cancer.

Integrins in development and cancer.

The correct control of cell fate decisions is critical for metazoan development and tissue homeostasis. It is established that the integrin family of cell surface receptors regulate cell fate by mediating cell-cell and cell-extracellular matrix (ECM) interactions. However, our understanding of how the different family members control discrete aspects of cell biology, and how this varies between tissues and is temporally regulated, is still in its infancy. An emerging area of investigation aims to understand how integrins translate changes in tension in the surrounding microenvironment into biological responses. This is particularly pertinent due to changes in the mechanical properties of the ECM having been linked to diseases, such as cancer. In this review, we provide an overview of the roles integrins play in important developmental processes, such as proliferation, polarity, apoptosis, differentiation and maintenance of "stemness". We also discuss recent advances in integrin mechanobiology and highlight the involvement of integrins and aberrant ECM in cancer.

Identification of functional networks of estrogen- and c-Myc-responsive genes and their relationship to response to tamoxifen therapy in breast cancer.

BACKGROUND: Estrogen is a pivotal regulator of cell proliferation in the normal breast and breast cancer. Endocrine therapies targeting the estrogen receptor are effective in breast cancer, but their success is limited by intrinsic and acquired resistance. METHODOLOGY/PRINCIPAL FINDINGS: With the goal of gaining mechanistic insights into estrogen action and endocrine resistance, we classified estrogen-regulated genes by function, and determined the relationship between functionally-related genesets and the response to tamoxifen in breast cancer patients. Estrogen-responsive genes were identified by transcript profiling of MCF-7 breast cancer cells. Pathway analysis based on functional annotation of these estrogen-regulated genes identified gene signatures with known or predicted roles in cell cycle control, cell growth (i.e. ribosome biogenesis and protein synthesis), cell death/survival signaling and transcriptional regulation. Since inducible expression of c-Myc in antiestrogen-arrested cells can recapitulate many of the effects of estrogen on molecular endpoints related to cell cycle progression, the estrogen-regulated genes that were also targets of c-Myc were identified using cells inducibly expressing c-Myc. Selected genes classified as estrogen and c-Myc targets displayed similar levels of regulation by estrogen and c-Myc and were not estrogen-regulated in the presence of siMyc. Genes regulated by c-Myc accounted for 50% of all acutely estrogen-regulated genes but comprised 85% (110/129 genes) in the cell growth signature. siRNA-mediated inhibition of c-Myc induction impaired estrogen regulation of ribosome biogenesis and protein synthesis, consistent with the prediction that estrogen regulates cell growth principally via c-Myc. The 'cell cycle', 'cell growth' and 'cell death' gene signatures each identified patients with an attenuated response in a cohort of 246 tamoxifen-treated patients. In multivariate analysis the cell death signature was predictive independent of the cell cycle and cell growth signatures. CONCLUSIONS/SIGNIFICANCE: These functionally-based gene signatures can stratify patients treated with tamoxifen into groups with differing outcome, and potentially identify distinct mechanisms of tamoxifen resistance.

Identification of downstream targets of estrogen and c-myc in breast cancer cells.

Estrogen (E) plays a pivotal regulatory role in the control of cell proliferation in the normal breast and breast cancer (BC). To identify genes with likely roles in proliferation control that are regulated by E and its downstream target c-myc, we compared transcript profiles of antiestrogens-arrested cells stimulated to reinitiate cell cycle progression by E treatment or c-myc induction. Approximately 2/3 of the probe sets significantly regulated by E (adjusted p < 0.01) increased in expression. Half of the E-regulated probe sets were also regulated by c-myc. Genes involved in cell growth, cell proliferation, and cell survival were over-represented in the E-regulated geneset. Analysis of selected candidates has identified a nucleolar protein whose expression is correlated with c-myc expression in BC cell lines. These data indicate that a significant component of E-induced mitogenesis is mediated by c-myc and that selected c-myc target genes may be surrogate markers of c-myc expression in BC.

The estrogen and c-Myc target gene HSPC111 is over-expressed in breast cancer and associated with poor patient outcome.

INTRODUCTION: Estrogens play a pivotal role in the initiation and progression of breast cancer. The genes that mediate these processes are not fully defined, but potentially include the known mammary oncogene MYC. Characterization of estrogen-target genes may help to elucidate further the mechanisms of estrogen-induced mitogenesis and endocrine resistance. METHODS: We used a transcript profiling approach to identify targets of estrogen and c-Myc in breast cancer cells. One previously uncharacterized gene, namely HBV pre-S2 trans-regulated protein 3 (HSPC111), was acutely upregulated after estrogen treatment or inducible expression of c-Myc, and was selected for further functional analysis using over-expression and knock-down strategies. HSPC111 expression was also analyzed in relation to MYC expression and outcome in primary breast carcinomas and published gene expression datasets. RESULTS: Pretreatment of cells with c-Myc small interfering RNA abrogated estrogen induction of HSPC111, identifying HSPC111 as a potential c-Myc target gene. This was confirmed by the demonstration of two functional E-box motifs upstream of the transcription start site. HSPC111 mRNA and protein were over-expressed in breast cancer cell lines and primary breast carcinomas, and this was positively correlated with MYC mRNA levels. HSPC111 is present in a large, RNA-dependent nucleolar complex, suggesting a possible role in ribosomal biosynthesis. Neither over-expression or small interfering RNA knock-down of HSPC111 affected cell proliferation rates or sensitivity to estrogen/antiestrogen treatment. However, high expression of HSPC111 mRNA was associated with adverse patient outcome in published gene expression datasets. CONCLUSION: These data identify HSPC111 as an estrogen and c-Myc target gene that is over-expressed in breast cancer and is associated with an adverse patient outcome.

c-Myc overexpression and endocrine resistance in breast cancer.

The oncoprotein c-Myc is frequently overexpressed in breast cancer and ectopic expression in breast cancer cell lines attenuates responses to antiestrogen treatment. Here, we review preliminary data aimed at further elucidating a potential role for c-Myc in clinical endocrine resistance in breast cancer. Immunohistochemical and semi-quantitative PCR revealed that c-Myc protein and c-myc mRNA were frequently overexpressed in both ER-positive and ER-negative breast carcinoma. Furthermore, both constitutive and inducible c-Myc overexpression in MCF-7 breast cancer cell lines markedly reduced their sensitivity to the growth inhibitory effects of the pure antiestrogen ICI 182,780. In order to identify potential downstream targets of c-Myc that mediate this effect, Affymetrix microarrays were employed to examine the patterns of gene expression shared by MCF-7 cells stimulated by estrogen, or by induction of c-Myc. Approximately 50% of estrogen target genes identified 6h after treatment were also regulated by c-Myc. One novel target, EMU4, was transcriptionally regulated by c-Myc. In addition, there was a strong correlation between c-myc and EMU4 mRNA expression in a battery of breast cancer cell lines. These data confirm that c-Myc overexpression is a common event in breast cancer, and that this is associated with resistance to antiestrogens in vitro. Furthermore, the development of an experimental paradigm for the discovery of c-Myc and estrogen target genes associated with endocrine resistance provides a framework for the discovery and validation of genes involved in estrogen signalling, and c-Myc-mediated-antiestrogen resistance.