The Hippo signaling pathway is a relatively young tumor-related signaling pathway. Although it was discovered lately, research on it developed rapidly. The Hippo signaling pathway is closely relevant to the occurrence and development of tumors and the maintenance of organ size and other biological processes. This manuscript focuses on YAP, the core molecule of the Hippo signaling pathway, and discussion the upstream and downstream regulatory networks of the Hippo signaling pathway during tumorigenesis and development. It also summarizes the relevant drugs involved in this signaling pathway, which may be helpful to the development of targeted drugs for cancer therapy.
BackgroundLong noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown.MethodsWe used the microarray data to identify differentially expressed lncRNAs between breast cancer and adjacent breast epithelial tissues. In vitro and in vivo assays were used to explore the biological effects of the differentially expressed lncRNA Apoptosis-Associated Transcript in Bladder Cancer (AATBC) in breast cancer cells. The mass spectrometry and RNA pulldown were used to screen AATBC interacting proteins. Using the Kaplan-Meier method, survival analysis was performed.ResultsThe expression of AATBC was significantly high in breast cancer samples, and this high AATBC level was tightly correlated with poor prognosis in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer cells migration and invasion. AATBC specifically interacted with Y-box binding protein 1 (YBX1), which activated the YAP1/Hippo signaling pathway by binding to macrophage stimulating 1 (MST1) and promoting the nuclear translocation of Yes associated protein 1 (YAP1), allowing its function as a nuclear transcriptional regulator. ConclusionsAATBC is highly expressed in breast cancer and contributes to patients’ progression, indicating that it could serve as a novel prognostic marker for the disease. Mechanistically, AATBC affects migration and invasion of breast cancer cells through an AATBC-YBX1-MST1 axis, resulting in activating the YAP1/Hippo signaling pathway. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of “AATBC-YAP1” may bring a new dawn to the treatment of breast cancer.
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