Search

Egg white (EW)‐derived hydrogels hold promise as biomaterials for in vitro cell culture due to their ability to mimic the extracellular matrix. However, their highly cross‐linked structures restrict their potential for in vivo applications, as they are unable to integrate dynamically with tissues before degradation. In this study, this limitation is addressed by introducing carbon dots (CDs) as cross‐linking agents for EW in a dilute aqueous solution. The resulting CDs‐crosslinked EW hydrogel (CEWH) exhibits tensile strength comparable to that of skin tissue and features a large pore structure that promotes cell infiltration. Subcutaneous implantation of CEWH demonstrated excellent integration with surrounding tissue and a degradation rate aligned with the hair follicles (HFs) regeneration cycle. This allows the long‐term regeneration and establishment of an M2 macrophage‐dominated immune microenvironment, which in turn promotes the re‐entry of HFs into the anagen phase from the telogen phase. Additionally, CEWH demonstrated potential as a wound dressing material. Overall, this study paves the way for utilizing EW as a versatile biomaterial for tissue engineering. [ABSTRACT FROM AUTHOR]

Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis of nucleotide precursors and amino acids. Inhibition of PGAM by small RNAi or small molecule attenuates cell proliferation and tumor growth. PGAM activity is commonly upregulated in tumor cells, but how PGAM activity is regulated in vivo remains poorly understood. Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. Increased levels of reactive oxygen species stimulate PGAM2 deacetylation and activity by promoting its interaction with SIRT2. Substitution of endogenous PGAM2 with an acetylation mimetic mutant K100Q reduces cellular NADPH production and inhibits cell proliferation and tumor growth. These results reveal a mechanism of PGAM2 regulation and NADPH homeostasis in response to oxidative stress that impacts cell proliferation and tumor growth.

Circulating tumor cells (CTCs) shed from primary tumors must overcome the cytotoxicity of immune cells, particularly natural killer (NK) cells, to cause metastasis. The tumor microenvironment (TME) protects tumor cells from the cytotoxicity of immune cells, which is partially executed by cancer‐associated mesenchymal stromal cells (MSCs). However, the mechanisms by which MSCs influence the NK resistance of CTCs remain poorly understood. This study demonstrates that MSCs enhance the NK resistance of cancer cells in a gap junction‐dependent manner, thereby promoting the survival and metastatic seeding of CTCs in immunocompromised mice. Tumor cells crosstalk with MSCs through an intercellular cGAS‐cGAMP‐STING signaling loop, leading to increased production of interferon‐β (IFNβ) by MSCs. IFNβ reversely enhances the type I IFN (IFN‐I) signaling in tumor cells and hence the expression of human leukocyte antigen class I (HLA‐I) on the cell surface, protecting the tumor cells from NK cytotoxicity. Disruption of this loop reverses NK sensitivity in tumor cells and decreases tumor metastasis. Moreover, there are positive correlations between IFN‐I signaling, HLA‐I expression, and NK tolerance in human tumor samples. Thus, the NK‐resistant signaling loop between tumor cells and MSCs may serve as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

The development of metastatic melanoma is thought to require the dynamic shifting of neoplastic cells between proliferative and invasive phenotypes. Contrary to this conventional 'phenotype switching' model, we now show that disease progression can involve malignant melanoma cells simultaneously displaying proliferative and invasive properties. Using a genetic mouse model of melanoma in combination with in vitro analyses of melanoma cell lines, we found that conditional deletion of the downstream signaling molecule Smad4, which abrogates all canonical TGF- [beta] signaling, indeed inhibited both tumor growth and metastasis. Conditional deletion of the inhibitory signaling factor Smad7, however, generated cells that are both highly invasive and proliferative, indicating that invasiveness is compatible with a high proliferation rate. In fact, conditional Smad7 deletion led to sustained melanoma growth and at the same time promoted massive metastasis formation, a result consistent with data indicating that low SMAD7 levels in patient tumors are associated with a poor survival. Our findings reveal that modulation of SMAD7 levels can overcome the need for phenotype switching during tumor progression and may thus represent a therapeutic target in metastatic disease., Introduction Despite recent progress in therapy, melanoma has remained by far the deadliest skin cancer, with a 5-year survival rate of only 15% to 20% (1). There is increasing evidence [...]

Cancer metastasis is the cause of the majority of cancer-related deaths. In this study, we demonstrated that no expression or low expression of ATP11B in conjunction with high expression of PTDSS2, which was negatively regulated by BRCA1, markedly accelerates tumor metastasis. Further analysis revealed that cells with low ATP11B expression and high PTDSS2 expression ([ATP11B.sup.lo][PTDSS2.sup.hi] cells) were associated with poor prognosis and enhanced metastasis in breast cancer patients in general. Mechanistically, an [ATP11B.sup.lo][PTDSS2.sup.hi] phenotype was associated with increased levels of nonapoptotic phosphatidylserine (PS) on the outer leaflet of the cell membrane. This PS increase serves as a global immunosuppressive signal to promote breast cancer metastasis through an enriched tumor microenvironment with the accumulation of myeloid-derived suppressor cells and reduced activity of cytotoxic T cells. The metastatic processes associated with [ATP11B.sup.lo][PTDSS2.sup.hi] cancer cells can be effectively overcome by changing the expression phenotype to [ATP11B.sup.hi][PTDSS2.sup.lo] through a combination of anti-PS antibody with either paclitaxel or docetaxel. Thus, blocking the [ATP11B.sup.lo][PTDSS2.sup.hi] axis provides a new selective therapeutic strategy to prevent metastasis in breast cancer patients., Introduction Breast cancer is the most common type of cancer and the second leading cause of cancer mortality among women in the world (1, 2). While the majority of breast [...]