The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial–mesenchymal transition, which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of phosphoglycerate dehydrogenase, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers. Significance: E-Cadherin promotes the progression and metastasis of breast cancer by upregulating the de novo serine synthesis pathway, offering promising targets for inhibiting tumor growth and metastasis in E-cadherin–expressing tumors.

In this study, we present a novel 3D perfused skin-on-a-chip model fabricated using micro-precision 3D printing, which offers a streamlined and reproducible approach for incorporating perfusion. Perfused skin models are well-regarded for their advantages, such as improved nutrient supply, enhanced barrier function, and prolonged tissue viability. However, current models often require complex setups, such as self-assembled endothelial cells or sacrificial rods, which are prone to variability and time-consuming. Our model uses projection micro-stereolithography 3D printing to create precise microcapillary-like channels using a biocompatible resin, overcoming the drug-absorbing properties of PDMS. A customized chip holder allows for the simultaneous culture of six perfused chips, enabling high-throughput testing. The engineered skin-on-a-chip features distinct dermis and epidermis layers, confirmed via H&E staining and immunostaining. To evaluate drug screening capabilities, inflammation was induced using TNF-α and treated with dexamethasone, with cytokine levels compared to 2D cultures and human skin biopsies. Our 3D model exhibited drug response trends similar to human skin, while showing reduced cytotoxicity over time compared to biopsies. This perfused skin-on-a-chip provides a reliable, physiologically relevant alternative for drug and cosmetics screening, simplifying perfusion setup while preserving key benefits.

Near-infrared (NIR) light (650 to 1700 nm) has been extensively used in various medical procedures and bioimaging with its unique physical properties. NIR light is featured with reduced scattering, minimal tissue absorption with high tissue penetration depth, and low tissue autofluorescence interference compared with visible light, and therefore suitable for bioimaging with high signal-to-background ratio and resolution of deep tissues.^{1 – 5} In addition, it shows minimum genotoxicity.⁶ These characteristics collectively favor the therapeutic use of NIR light in the clinic. In fact, since low power NIR light, typically 1 mW to $5\mathrm{W}/{\mathrm{cm}}^2$, shows diverse biological effects, including pain relief, facilitation of tissue regeneration, and reduction of the inflammation,^{7 – 11} which is broadly defined as photobiomodulation, the use of NIR light has been explored for a wide array of therapeutic purposes during the past decades.¹⁰

Aging is a progressive functional decline in organs and tissues over time and typically represents the accumulation of psychological and social changes in a human being. Diverse diseases, such as cardiovascular, musculoskeletal, and neurodegenerative disorders, are now understood to be caused by aging. While biological assessment of aging mainly focuses on the gradual changes that occur either on the molecular scale, for example, alteration of gene expression and epigenetic modification, or on larger scales, for example, changes in muscle strength and cardiac function, the mechanics that regulates the behavior of individual cells and interactions between the internal elements of cells, are largely missing. In this study, we show that the dynamic features of migrating cells across different human ages could help to establish the underlying mechanism of biological age-dependent cellular functional decline. To determine the relationship between cellular dynamics and human age, we identify the characteristic relationship between cell migration and nuclear motion which is tightly regulated by nucleus-bound cytoskeletal organization. This analysis demonstrates that actomyosin contractility-dependent nuclear motion plays a key role in cell migration. We anticipate this study to provide noble biophysical insights on biological aging in order to precisely diagnose age-related chronic diseases.

The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial–mesenchymal transition, which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of phosphoglycerate dehydrogenase, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.Significance: E-Cadherin promotes the progression and metastasis of breast cancer by upregulating the de novo serine synthesis pathway, offering promising targets for inhibiting tumor growth and metastasis in E-cadherin–expressing tumors.

The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial–mesenchymal transition, which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of phosphoglycerate dehydrogenase, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.Significance:E-Cadherin promotes the progression and metastasis of breast cancer by upregulating the de novo serine synthesis pathway, offering promising targets for inhibiting tumor growth and metastasis in E-cadherin–expressing tumors.