Recognition of pathogen-associated molecular patterns (PAMPs) triggers expression of antiviral interferons and proinflammatory cytokines, which functions as the frontier of host defense against microbial pathogen invasion. Hippo-YAP pathway regulates cell proliferation, survival, differentiation and is involved in diverse life processes, including tissue homeostasis and tumor suppression. Emerging discoveries elucidated that the components of Hippo-YAP pathway, such as MST1/2, NDR1/2, and YAP/TAZ played crucial regulatory roles in innate immunity. Meanwhile the innate immune signaling also exhibited regulatory effect on Hippo-YAP pathway. As for the importance of these two pathways, it would be interesting to figure out the deeper biological implications of their interplays. This review focuses on the regulation between Hippo-YAP pathway and innate immune signaling. We also propose the possible contribution of these interplays to tumor development.
Cancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-β type II receptor (TβRII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-β signaling in recipient cells. Up-take of extracellular vesicle-TβRII (EV-TβRII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-TβRII delivered as cargo to CD8+ T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8+ T cell exhaustion, resulting in failure of immunotherapy. The levels of TβRII+ circulating extracellular vesicles (crEV) appears to correlate with tumor burden, metastasis and patient survival, thereby serve as a non-invasive screening tool to detect malignant breast tumor stages. Thus, our findings not only identify a possible mechanism by which breast cancer cells can promote T cell exhaustion and dampen host anti-tumor immunity, but may also identify a target for immune therapy against the most devastating breast tumors.
Drug resistance is a major challenge in breast cancer (BC) treatment at present. Accumulating studies indicate that breast cancer stem cells (BCSCs) are responsible for the BC drugs resistance, causing relapse and metastasis in BC patients. Thus, BCSCs elimination could reverse drug resistance and improve drug efficacy to benefit BC patients. Consequently, mastering the knowledge on the proliferation, resistance mechanisms, and separation of BCSCs in BC therapy is extremely helpful for BCSCs-targeted therapeutic strategies. Herein, we summarize the principal BCSCs surface markers and signaling pathways, and list the BCSCs-related drug resistance mechanisms in chemotherapy (CT), endocrine therapy (ET), and targeted therapy (TT), and display therapeutic strategies for targeting BCSCs to reverse drug resistance in BC. Even more importantly, more attention should be paid to studies on BCSC-targeted strategies to overcome the drug resistant dilemma of clinical therapies in the future.
Female breast cancer is a complex, multifactorial disease. Studies have shown that hyperglycemia is one of the most important contributing factors to increasing the risk of breast cancer that also has a major impact on the efficacy of chemotherapy. At the cellular level, hyperglycemia can promote the proliferation, invasion, and migration of breast cancer cells and can also induce anti-apoptotic responses to enhance the chemoresistance of tumors via abnormal glucose metabolism. In this article, we focus on the latest progress in defining the mechanisms of chemotherapy resistance in hyperglycemic patients including the abnormal behaviors of cancer cells in the hyperglycemic microenvironment and the impact of abnormal glucose metabolism on key signaling pathways. To better understand the advantages and challenges of breast cancer treatments, we explore the causes of drug resistance in hyperglycemic patients that may help to better inform the development of effective treatments.
It has been reported that lncRNA POU3F3 was upregulated in esophageal squamous-cell carcinomas, indicating its role as an oncogene in this disease. However, the mechanism of its function and its involvement in other malignancies is unknown. In the present study we found that expression levels of lncRNA POU3F3 were higher in tumor tissues than in adjacent healthy tissues of triple negative breast cancer (TNBC) patients and were significantly and inversely correlated with levels of cleaved caspase 9 only in tumor tissues. In addition, plasma levels of lncRNA POU3F3 were higher in TNBC patients than in healthy controls and were significantly and inversely correlated with levels of cleaved caspase 9 only in TNBC patients. In addition, treatment of exogenous Cleaved Caspase-9 significantly attenuated the effects of lncRNA POU3F3 overexpression on cancer cell proliferation and apoptosis. lncRNA POU3F3 may promote proliferation and inhibit apoptosis of cancer cells in triple-negative breast cancer.
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