Molecular Cancer最新文献

Tumor precision treatment still faces the challenge of being unable to achieve real-time monitoring. The rapid advancements in nanomedicine within the biomedical sector have highlighted the potential of integrated nano-platforms for tumor diagnosis and treatment. Herein, we create a multimodal diagnostic nanodrug, ⁹⁹^mTc-NP^AIE-MSA, which combines sonosensitizers, STING agonists, and radionuclides for immuno-sonodynamic therapy targeting breast cancer. This platform utilizes polymers with aggregation-induced luminescence properties that, when activated by US, generate cytotoxic reactive oxygen species, causing DNA and mitochondrial damage, activating the cGAS-STING pathway, and releasing the STING agonist MSA-2 to enhance the immune response. Additionally, ⁹⁹^mTc incorporation facilitates SPECT/CT and near-infrared fluorescence imaging, thereby improving tumor targeting and therapeutic monitoring precision. Both in vitro and in vivo studies confirm the significant anti-tumor effects and immunomodulation achieved by this nano-platform under US, presenting a novel strategy for precise tumor diagnosis and treatment.

Ovarian cancer (OC) is the predominant gynecological cancer and is associated with severe morbidity and high mortality worldwide. Therefore, clarifying the molecular mechanisms underlying OC progression and exploring novel therapeutic targets are important. Here, using human OC samples, different OC cell lines, and xenograft nude mouse models in combination with multiple sequencings, we report that hnRPD, an RNA binding protein that modulates RNA stability, is highly expressed in OC tissues, and contributes to OC cell malignancy in human OC cells cultured in vitro and in OC cell-derived xenograft nude mouse models in vivo. Mechanistically, ectopically expressed GPR137 binds to hnRPD and enhances hnRPD protein stability, which reciprocally transactivates GPR137 through the transcription factor FLI1. On the other hand, elevated hnRPD upregulates RAB8A expression by interacting with RAB8A mRNA and promoting its stability, leading to activation of downstream cell signaling and thereby enhanced OC cell malignant behaviors including cell proliferation, cell invasion, cell migration, and colony formation ability as well as OC xenograft growth in nude mice. Moreover, cisplatin in combination with silencing of hnRPD expression, significantly induces apoptosis in cisplatin-resistant OC cells through regulation of OC cell metabolism. Therefore, our data provide evidence that hnRPD could represent an innovative prognostic indicator for OC and may be an attractive therapeutic target for improving clinical outcomes in OC treatment.

Background: Growing evidence highlights the existence and tumor-promoting role of intratumoral bacteria in various types of cancers. However, the mechanisms enabling the intracellular survival of these microorganisms remain poorly understood, impeding the development of microbiota-targeting anticancer strategies.

Methods: A transcriptomics analysis was used to identify the disease-related bacteria in nasopharyngeal carcinoma (NPC). Cell-bacteria coculture assay, cell viability assay, and mouse xenograft tumor model were used for functional investigation. Immunofluorescence, quantitative PCR analysis, RNA sequencing, immunoblot analysis, co-immunoprecipitation and mass spectrometry were utilized in mechanistic research. Fluorescent in situ hybridization in NPC specimens and clinical data were used for prognosis analysis.

Results: We discovered that the Fusobacterium nucleatum (F. nucleatum), especially the C2 clade of F. nucleatum subsp. animalis (Fna C2), acts as an intracellular pathogen and exhibits distinct colonization advantages in NPC by inhibiting autophagy flux in host cells. Mechanistically, the virulence protein FadA of Fna C2 increases the ubiquitination and promotes the degradation of Ras-related protein RAB7A by enhancing the interaction between RAB7A and the E3 ligase TRIM28, which thus impairs the autophagosome-lysosome fusion and the autophagy machinery. The dysfunctional autophagy not only enables the persistent intracellular survival of F. nucleatum but also contributes to the treatment resistance of NPC. Clinically, a high intratumoral F. nucleatum colonization is associated with tumor relapse and poor outcome in NPC patients.

Conclusion: Our findings elucidate a key mechanism by which F. nucleatum survives and promotes treatment resistance in NPC, providing a microbiological prognosis indicator for NPC patients.