YAP/TAZ axis was involved in the effects of metformin on breast cancer.

Breast cancer is malignant tumours in women. A large amount of data analysis shows that Metformin has been shown to play a significance role in reducing the risk of breast cancer, but the mechanism remains unclear. The hippo signalling pathway can be involved in the formation, metastasis and recurrence of breast cancer. When YAP/TAZ is activated, cells can overcome contact inhibition and enter a state of uncontrolled proliferation. Therefore, YAP/TAZ is considered a potential therapeutic target for breast cancer. Eighty breast cancer patients, forty cases of triple-negative and forty cases of HER-2+, were included in this study. In vitro and in vivo experiments were used to confirm the YAP/TAZ axis was involved in the effects of metformin on breast cancer. EMT plays an important role in breast cancer, including chemoresistance and tumour metastasis. Our results confirmed that YAP could modulate the activity of EMT, which in turn altered tumour resistance. Therefore, MET can inhibit EMT by reducing the expression of YAP, and finally achieve the therapeutic effect of breast cancer. Our findings support metformin as a novel YAP inhibitor and potentially as a novel breast cancer drug.

Astrocytes promote the proliferation of oligodendrocyte precursor cells through connexin 47-mediated LAMB2 secretion in exosomes.

BACKGROUND: Oligodendrocyte precursor cells (OPCs) can proliferate and differentiate into oligodendrocytes, the only myelin-forming cells in the central nervous system. Proliferating OPCs promotes remyelination in neurodegenerative diseases. Astrocytes (ASTs) are the most widespread cells in the brain and play a beneficial role in the proliferation of OPCs. Connexin 47 (Cx47) is the main component of AST-OPC gap junctions to regulate OPC proliferation. Nonetheless, the specific mechanism remains unclear. METHODS AND RESULTS: This study investigates the proliferation mechanism of OPCs connected to ASTs via Cx47. Cx47 siRNA significantly inhibited OPCs from entering the proliferation cycle. Transcriptome sequencing of OPCs and gene ontology enrichment analysis revealed that ASTs enhanced the exosome secretion by OPCs via Cx47. Transmission electron microscopy, Western blot, and nanoparticle tracking analysis indicated that the OPC proliferation was related to extracellular exosomes. Cx47 siRNA decreased the OPC proliferation and exosome secretion in AST-OPC cocultures. Exogenous exosome supplementation alleviated the inhibitory effect of Cx47 siRNA and significantly improved OPC proliferation. Mass spectrometry revealed that LAMB2 was abundant in exosomes. The administration of exogenous LAMB2 induced DNA replication in the S phase in OPCs by activating cyclin D1. CONCLUSIONS: Collectively, ASTs induce the secretion of exosomes that carry LAMB2 by OPCs via Cx47 to upregulate cyclin D1 thereby accelerating OPC proliferation.

Tubeimoside-I sensitizes colorectal cancer cells to chemotherapy by inducing ROS-mediated impaired autophagolysosomes accumulation.

BACKGROUND: Tubeimoside-I (TBM), a plant-derived bioactive compound, shows antitumor activity in different tumors and can enhance the efficacy of chemotherapeutic agents. However, the detail mechanism underlying remains to be elucidated. METHODS: The cytotoxic potential of TBM towards CRC cells was examined by CCK8 assay, colony formation, LDH release assay, flow cytometry method and Western blots. The ROS levels, autophagy, apoptosis, chemosensitivity to 5-FU or DOX, etc. were determined between control and TBM-treated CRC cells. RESULTS: In this study, we found that TBM could inhibit proliferation and induce apoptosis in colorectal cancer (CRC) cells. Intriguingly, TBM treatment could either promote autophagy initiation by ROS-induced AMPK activation, or block autophagy flux through inhibiting lysosomal hydrolytic enzymes, which leaded to massive impaired autophagylysosomes accumulation. Administration of autophagy initiation inhibitor (3-MA or selective ablation of autophagy related proteins) relieves TBM-induced CRC suppression, while combination use of autophagy flux inhibitor chloroquine (CQ) slightly augments TBM-induced cell death, suggesting that impaired autophagylysosomes accumulation contributes to TBM-induced growth inhibition in CRC cells. Notably, as an autophagy flux inhibitor, TBM works synergistically with 5-fluorouracil (5-FU) or doxorubicin (DOX) in CRC suppression. CONCLUSION: Together, our study provides new insights regarding the anti-tumor activity of TBM against CRC, and established potential applications of TBM for CRC combination therapies in clinic.