STX3 represses the stability of the tumor suppressor PTEN to activate the PI3K-Akt-mTOR signaling and promotes the growth of breast cancer cells
| Autor: | Jiequn Ma, Rujuan Su, Lili Han, Jianjun He, Chengcheng Yang, Haocheng Nan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Breast Neoplasms Ipatasertib 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Breast cancer Ubiquitin medicine PTEN Humans skin and connective tissue diseases Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Gene knockdown biology Qa-SNARE Proteins TOR Serine-Threonine Kinases PTEN Phosphohydrolase Middle Aged medicine.disease Syntaxin 3 Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein MCF-7 Cells Molecular Medicine Female Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochimica et biophysica acta. Molecular basis of disease. 1864(5 Pt) |
| ISSN: | 0925-4439 |
| Popis: | Syntaxin 3, also known as STX3, is a protein encoded by the STX3 gene in humans. This protein is one of the fundamental components of the exocytotic machinery required for the docking and fusion of secretory granules with the plasma membrane. The roles of STX3 in human breast cancer remains elusive. Here we report that STX3 acts as an oncogenic protein in human breast cancer. We analyzed the expression of STX3 in 148 patients with breast cancer. The mRNA and protein levels of STX3 are significantly up-regulated in human breast cancer compared with matched adjacent non-cancer tissues. The up-regulation of STX3 is correlated with high disease stage and predicts overall and disease-free survival in patients with breast cancer. Lentivirus-mediated knockdown of STX3 represses in vitro proliferation and colony formation and in vivo growth of breast cancer cells, whereas STX3 overexpression promotes the growth of breast cancer cells in vitro and in vivo. We find that STX3 promotes the proliferation of breast cancer cells by increasing the activation of the Akt-mTOR signaling, and Akt inhibitor Ipatasertib or MK-2206 represses STX3 effects on the growth of breast cancer cells. Further mechanism study shows that STX3 binds to PTEN and increases PTEN ubiquitination and degradation, thus leading to activation of the PI3K-Akt-mTOR signaling. Therefore, STX3 promotes the growth of breast cancer cells by regulating the PTEN-PI3K-Akt-mTOR signaling. |
| Databáze: | OpenAIRE |
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