COL5A1 promotes triple-negative breast cancer progression by activating tumor cell-macrophage crosstalk.

Triple-negative breast cancer (TNBC) is an exceptionally aggressive subtype of breast cancer. Despite the recognized interplay between tumors and tumor-associated macrophages in fostering drug resistance and disease progression, the precise mechanisms leading these interactions remain elusive. Our study revealed that the upregulation of collagen type V alpha 1 (COL5A1) in TNBC tissues, particularly in chemoresistant samples, was closely linked to an unfavorable prognosis. Functional assays unequivocally demonstrated that COL5A1 played a pivotal role in fueling cancer growth, metastasis, and resistance to doxorubicin, both in vitro and in vivo. Furthermore, we found that the cytokine IL-6, produced by COL5A1-overexpressing TNBC cells actively promoted M2 macrophage polarization. In turn, TGFß from M2 macrophages drived TNBC doxorubicin resistance through the TGFß/Smad3/COL5A1 signaling pathway, establishing a feedback loop between TNBC cells and macrophages. Mechanistically, COL5A1 interacted with TGM2, inhibiting its K48-linked ubiquitination-mediated degradation, thereby enhancing chemoresistance and increasing IL-6 secretion. In summary, our findings underscored the significant contribution of COL5A1 upregulation to TNBC progression and chemoresistance, highlighting its potential as a diagnostic and therapeutic biomarker for TNBC.

Blue- and green-emitting hydrophobic carbon dots: preparation, optical transition, and carbon dot-loading.

In the past decade, hydrophobic fluorescent carbon dots (OCDs) have received little attention, and its potential application and light transition mechanism is seldom explored. Here we report a novel one-step approach for synthesizing blue- and green-emitting hydrophobic fluorescent carbon dots (OCDb and OCDg) by calcinating with the uses of citric acid and hexadecylamine as initial reactants. The optimal conditions for preparing OCDb and OCDg were obtained by using the Taguchi L25 (35) orthogonal array. The highest quantum yield and product yield of OCDs reached 80.2% and 57.1%, respectively, larger than those from most of all the known reports. The fluorescent stability of OCDb and OCDg was excellent under UV irradiation (30 W) for days. The luminescent color of OCDs showed a great dependence on reaction conditions. It is easier to get OCDg via a reaction kept at a high temperature for a long time. The optical transition mechanism was studied for the two kinds of color OCDs, and therefore proposed in combination with their optical properties and surface groups. The reason for light transition is probably related to an appropriate critical ratio and surface density of the C=O and N-H bond in the surface structure of the product. For the OCDg, the concentration matching ratio of N-H and C=O bonds in the surface structure of the green-emitting product is approximately between d/2 and 3d/2, where d is a fixed constant. Lower than or higher than this critical ratio range, the product emits blue light. Based on their high fluorescence quantum efficiency and the advantages mentioned above, these OCDs were then respectively used for preparing hydrophobic fluorescent carbon dot-loading liposomes and acrylate films, both exhibiting a perfect performance with no fluorescence quenching.