Table1_The Prognostic Model and Drug Sensitivity of LKB1-Mutant Lung Adenocarcinoma Based on Immune Landscape.DOCX

Background: Lung cancer is the most common cause of cancer-related deaths worldwide. LKB1-mutant lung adenocarcinoma (LUAD) is a unique subtype of this deadly cancer. LKB1 mutations cause functional changes in a variety of cell processes, including immune functions, that affect prognosis. To date, the potential role of immunity in the prognosis of LKB1-mutant LUAD is not well understood.Methods: We systematically analyzed immune-related genes in LUAD samples from The Cancer Genome Atlas (TCGA) database. ESTIMATE and CIBERSORT algorithms were used to explore the immune microenvironment. A prognostic risk model was constructed, and prognostic, immune function, drug sensitivity, and model specificity analyses were performed to identify the effectiveness of the model.Results: Our results showed that LKB1 mutations suppressed immune function in LUAD. A three-gene signature was constructed to stratify patients into two risk groups. The risk score was an independent predictor for overall survival (OS) in multivariate Cox regression analyses [hazard ratio (HR) > 1, p = 0.002]. Receiver operating characteristic (ROC) curve analyses confirmed that the risk score has better performance than clinicopathological characteristics. Functional analysis revealed that the immune status was different between the risk groups. ZM.447439 was an appropriate treatment for the high-risk group of patients. This risk model is only suitable for LKB1-mutant tumors; it performed poorly in LUAD patients with wild-type LKB1.Conclusion: Our findings indicate the potential role of immunity in LKB1-mutant LUAD, providing novel insights into prognosis and guiding effective immunotherapy.</p

Table1_The role of cell-matrix adhesion and cell migration in breast tumor growth and progression.DOCX

During breast cancer progression, there is typically increased collagen deposition resulting in elevated extracellular matrix rigidity. This results in changes to cell-matrix adhesion and cell migration, impacting processes such as the epithelial-mesenchymal transition (EMT) and metastasis. We aim to investigate the roles of cell-matrix adhesion and cell migration on breast tumor growth and progression by studying the impacts of different types of extracellular matrices and their rigidities. We embedded MCF7 spheroids within three-dimensional (3D) collagen matrices and agarose matrices. MCF7 cells adhere to collagen but not agarose. Contrasting the results between these two matrices allows us to infer the role of cell-matrix adhesion. We found that MCF7 spheroids exhibited the fastest growth rate when embedded in a collagen matrix with a rigidity of 5.1 kPa (0.5 mg/mL collagen), whereas, for the agarose matrix, the rigidity for the fastest growth rate is 15 kPa (1.0% agarose) instead. This discrepancy is attributable to the presence of cell adhesion molecules in the collagen matrix, which initiates collagen matrix remodeling and facilitates cell migration from the tumor through the EMT. As breast tumors do not adhere to agarose matrices, it is suitable to simulate the cell-cell interactions during the early stage of breast tumor growth. We conducted further analysis to characterize the stresses exerted by the expanding spheroid on the agarose matrix. We identified two distinct MCF7 cell populations, namely, those that are non-dividing and those that are dividing, which exerted low and high expansion stresses on the agarose matrix, respectively. We confirmed this using Western blot which showed the upregulation of proliferating cell nuclear antigen, a proliferation marker, in spheroids grown in the 1.0% agarose (≈13 kPa). By treating the embedded MCF7 spheroids with an inhibitor or activator of myosin contractility, we showed that the optimum spheroids’ growth can be increased or decreased, respectively. This finding suggests that tumor growth in the early stage, where cell-cell interaction is more prominent, is determined by actomyosin tension, which alters cell rounding pressure during cell division. However, when breast tumors begin generating collagen into the surrounding matrix, collagen remodeling triggers EMT to promote cell migration and invasion, ultimately leading to metastasis.</p

Phototunable Supersoft Elastomers using Coumarin Functionalized Molecular Bottlebrushes for Cell-Surface Interactions Study

Phototunable supersoft elastomers were prepared by photo-cross-linking molecular bottlebrushes with poly­(<i>n</i>-butyl acrylate) (PBA) side chains. Bottlebrushes were synthesized by atom transfer radical polymerization (ATRP) and Br-chain end functionalities were replaced by photo-cross-linkable coumarin units. Photo-cross-linking and photoscission of molecular bottlebrushes resulted in tunable elastomeric behavior quantified by dynamic mechanical analysis. The cell–substrate interactions, tuned by UV-light, depended on surface morphology and softness that could be as low as several kilopascals