Epidermal growth factor (EGF) mediates breast cancer cell chemotaxis and metastasis through mechanisms that involve the growth-regulatory mammalian target of rapamycin (mTOR) complex mTORC2, but the mechanisms involved remain obscure. Here, we report that the rapamycin-insensitive mTORC2 component protein Rictor is a critical mediator of metastasis in breast cancer cells. In patients with ductal carcinoma, Rictor expression was associated with increased lymph node metastasis. EGF induced translocation and colocalization of Rictor with protein kinase Cζ (PKCζ), a pivotal molecule in chemotaxis signaling. Further, Rictor coimmunoprecipitated with PKCζ in the absence of the mTORC2 complex. Small interfering RNAmediated knockdown of Rictor inhibited EGF-induced PKCζ phosphorylation and translocation along with phosphorylation of the key F-actin binding protein cofilin. In parallel, Rictor knockdown reduced cellular chemotactic capacity and ablated pulmonary metastasis in a xenograft mouse model of breast cancer. Our findings identify Rictor as an important mediator of chemotaxis and metastasis in breast cancer cells.
Obesity is a consideration in the pharmacologic intervention for estrogen receptor‐positive breast cancer risk. This case‐control study among women in Northern and Eastern China was conducted to clarify the possible associations between both general and central obesity and breast cancer risk.
Lung cancer is the most common type of cancer and the leading cause of death in worldwide. MicroRNAs are known to be key players in a variety of biological processes, including tumorigenesis. In present study, we investigated the effect of miR-361-5p on lung cancer progression. We found that miR-361-5p was down-regulated in lung cancer. Overexpression of miR-361-5p suppressed lung cancer proliferation and invasion. Mechanistically, FOXM1 was identified as a direct target of miR-361-5p. Furthermore, miR-361-5p inhibits EMT-like phenotype through down-regulation of FOXM1 expression in lung cancer cells. In conclusion, our results indicated that miR-361-5p acts as a tumor suppressor in lung cancer.
Occult breast carcinoma presenting axillary metastases is uncommon and accounts for less than 1% of newly diagnosed breast carcinoma. However, it continues to be a challenging diagnostic and therapeutic problem. In this study, we analyzed retrospectively on 51 cases of occult breast cancer from 1990 to 2003 in our hospital. All these patients had a palpable axillary nodule, no dominant breast mass, and no abnormal mammograms and breast ultrasonograph. Histological examination of axillary mass revealed metastasis from breast. The positive rate of estrogen receptor, progesterone receptor and the monoclonal antibody M4G3 against human breast cancer showed 62.7%, 66.7%, and 93.1% positive respectively. Among 51 cases, 38 cases received mastectomy whereas 13 cases had no local treatment of the breast. The primary tumors were detected in 28 of 38 cases having mastectomy by pathology. Seventy-seven percent of patients who had no local treatment of the breast had a tumor recurrence, compared with 26% who had a mastectomy. The mean disease-free survival was 23 months in patients who had no local treatment of the breast, compared with 76 months in patients who had mastectomy. Eight of the 13 patients who had no treatment with breast died whereas seven of the 38 who had local treatment died, with a mean follow-up of 73 months. It was found that patients having mastectomy had a better disease-free survival (p < 0.001) and overall survival (p < 0.001) compared with those having no local treatment of the breast. Once the diagnosis of occult breast carcinoma is clarified, an axillary dissection and the local treatment of breast should be carried out.
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