Soft tissue tumors, including breast cancer, become stiffer throughout disease progression. This increase in stiffness has been shown to correlate to malignant phenotype and epithelial-to-mesenchymal transition (EMT) in vitro. Unlike current models, utilizing static increases in matrix stiffness, our group has previously created a system that allows for dynamic stiffening of an alginate–matrigel composite hydrogel to mirror the native dynamic process. Here, we utilize this system to evaluate the role of matrix stiffness on EMT and metastasis both in vitro and in vivo. Epithelial cells were seen to lose normal morphology and become protrusive and migratory after stiffening. This shift corresponded to a loss of epithelial markers and gain of mesenchymal markers in both the cell clusters and migrated cells. Furthermore, stiffening in a murine model reduced tumor burden and increased migratory behavior prior to tumor formation. Inhibition of FAK and PI3K in vitro abrogated the morphologic and migratory transformation of epithelial cell clusters. This work demonstrates the key role extracellular matrix stiffening has in tumor progression through integrin signaling and, in particular, its ability to drive EMT-related changes and metastasis.
Various methods to determine the connectivity scores between groups of proteins associated with lung adenocarcinoma are examined. Proteins act together to perform a wide range of functions within biological processes. Hence, identification of key proteins and their interactions within protein networks can provide invaluable information on disease mechanisms. Differential network analysis provides a means of identifying differences in the interactions among proteins between two networks. We use connectivity scores based on the method of partial least squares to quantify the strength of the interactions between each pair of proteins. These scores are then used to perform permutation-based statistical tests. This examines if there are significant differences between the network connectivity scores for individual proteins or classes of proteins. The expression data from a study on lung adenocarcinoma is used in this study. Connectivity scores are computed for a group of 109 subjects who were in the complete remission and as well as for a group of 51 subjects whose cancer had progressed. The distributions of the connectivity scores are similar for the two networks yet subtle but statistically significant differences have been identified and their impact discussed.
Hira Singh's monograph Recasting Caste, is an important contribution to the field of sociology of caste, which uses a nuanced Marxist perspective to conclude that "sociologists of caste have invoked religion, cognition, cosmology…to find the secret of the genesis, growth, and survival of caste and the caste system. In the process, they have missed the real secret of caste and the caste system, which lies in the intersection of political economy and ideology" (16). Singh demonstrates how the economic infrastructure intersects with the cultural superstructure to (re)produce the practice and hegemony of caste based inequalities. Singh intervenes in an area, which has been dominated by the orientalist and colonial view of caste. The orientalist-colonial sociology of caste (e.g., Weber and Dumont) helped to introduce first a discourse of backwardness, and secondly a discourse of differentiation in the study of South Asia (Bandyopadhyay 2004: 11). Recasting Caste not only revives the Marxist analysis (Kumar 1965; Mencher 1974) of caste, but it also takes it further by introducing a transnational analysis of caste to the Marxist framework. The book is divided into seven chapters, the first three of which are Singh's critique of the orientalist-colonial sociology of caste. Singh argues that caste is a system of inequality, which is based on unequal access to the material conditions (e.g., land) of existence. Drawing on archival evidence, Singh also shows that the legitimation of the profane kingship was in its essence a political rather than a religious phenomenon as theorized by Dumont. The decisive factor in legitimizing kingship was the legitimation of the authority of the prince by his peers-the fraternity of landlords, members of his own caste and kin group, who were different and distant from the "sacred" priestly caste. After having established, that the Weberian and Dumontian sociological theories of caste mystify caste by masking the material foundation of caste inequality i.e. the inequality of land relations and the corresponding inequalities of access to political and cultural resources (63-105), Singh moves on to critically examine the scholarship on caste produced by the Subaltern Studies group. This examination is a solid
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.