Derlin-1 functions as a growth promoter in breast cancer.

Breast cancer is one of the most common malignant tumors in women. Derlin-1 has been found to be overexpressed in several human cancers in addition to playing an important role in tumor processes; however, the expression patterns and functions of Derlin-1 in human breast cancer are not fully understood. In this study, we found that Derlin-1 overexpression was higher in breast cancer compared to normal samples through TCGA and GTEx database analyses. Kaplan-Meier plotter analysis showed that Derlin-1 was a predicting factor for patient prognosis. Derlin-1 expression was significantly up-regulated in breast cancer tissues (18/30, 60.00%) compared to corresponding paracancerous tissue (9/30, 30.00%, p < 0.05) as detected by immunohistochemistry, and the expression of Derlin-1 was correlated to pathological grading. siRNA interference of Derlin-1 inhibited cell proliferation, which is associated with the promotion of apoptosis and migration. Derlin-1 knockdown suppressed the protein levels of p-AKT and Cyclin D1 while up-regulating Caspase3 and Bax. GEPIA database analysis showed that MTDH and ATAD2 were downstream target genes, and the expression of MTDH and was suppressed in Derlin-1 knockdown cells. Taken together, our results demonstrated ATAD2 that Derlin-1 is overexpressed in breast cancer and promoted a malignant phenotype through the AKT signaling pathway.

The overexpression of Rab9 promotes tumor progression regulated by XBP1 in breast cancer.

BACKGROUND: Rab9 is a small GTPase that localizes to the trans-Golgi Network (TGN) and late endosomes and is involved in the recycling of mannose-6-phosphate receptors (MPRs). MATERIALS AND METHODS: To determine new treatment strategies for breast cancer and to elucidate the mechanism underlying the phenomenon, we investigated the effects of Rab9 in the human breast cancer cell lines MCF7 and MDA-MB-231. RESULTS: We observed that knockdown of Rab9 inhibited the survival and proliferation of MCF7 and MDA-MB-231 cells, whereas Rab9 overexpression facilitated cell survival and proliferation by inducing or suppressing apoptosis. These results were further confirmed by the Bax/Bcl-2 ratio in affected MCF7 and MDA-MB-231 cells, which demonstrated whether the mitochondrial apoptotic pathway was triggered. Furthermore, the AKT/PI3K pathway is implicated in cell growth and survival and Rab9 changed the expression and phosphorylation of PI3K signaling pathway members. XBP1 is a key regulator of Rab9 and further confirmed that Rab9 play important roles in breast cancer tumorigenesis. CONCLUSION: These data suggest that Rab9 is a good candidate for a novel therapeutic strategy for the treatment of breast cancer.