The small GTPase Rab34 regulates spatial distribution of the lysosomes, secretion, and macropinocytosis. In this study, we found that Rab34 is over-expressed in aggressive breast cancer cells, implying a potential role of Rab34 in breast cancer. Silencing Rab34 by shRNA inhibits cell migration, invasion, and adhesion of breast cancer cells. Rab34 specifically binds to the cytoplasmic tail of integrin β3, and depletion of Rab34 promotes the degradation of integrin β3. Interestingly, EGF induces the translocation of Rab34 to the membrane ruffle, which is greatly enhanced by the expression of Src kinase. Accordingly, Rab34 is tyrosine phosphorylated by Src at Y247 residue. A mutant mimicking phosphorylated form of Rab34 (Rab34Y247D) promotes cell migration and invasion. Importantly, the tyrosine phosphorylation of Rab34 is inhibited in cells in suspension, and increased with the cells re-adhesion. In addition, Rab34Y247D promotes cell adhesion, and enhances integrin β3 endocytosis and recycling. The results uncover a role of Rab34 in migration and invasion of breast cancer cells and its involvement in cancer metastasis, and provide a novel mechanism of tyrosine phosphorylation of Rab34 in regulating cell migration, invasion, and adhesion through modulating the endocytosis, stability, and recycling of integrin β3.
Backgrounds Surgical resection of large primary breast tumor often results in large chest wall defects. The purpose of this study is to evaluate the feasibility of using adjacent skin rotation (ASR) flap in patients with giant primary breast tumor. Methods A total of 26 giant primary breast tumor patients treated with ASR flap were included in this study. The postoperative conditions, including operating time, blood loss, length of hospital stay, and clinical complications were observed. Meanwhile, the information on 17 breast tumor patients treated with transverse rectus abdominis myocutaneous (TRAM) flap were collected and assigned to a control group. Results The mean defect size after mastectomy was 16.7 × 13.4 cm, while the median follow‐up period was 13 months after surgery. A total of 15.4% patients had developed with local complications, and one of them had more than one complication. When comparing the postoperative outcomes, statistically significant differences were found between the two groups with respect to operating time, blood loss, and length of hospital stay (P < 0.001). Conclusions ASR flap is a reliable technique for immediate reconstruction of massive chest wall defects in patients with giant primary breast tumor.
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