Decreased Expression of Rab11a Promoted MDA-MB-468 Breast Cancer Cells Migration in a Hypoxic Environment

Abstract

Background: Hypoxia induces microenvironmental changes in breast cancer and other solid tumors. Tumor cells that survive hypoxia are claimed to acquire more aggressive properties through a cascade of activated signaling pathways. Here in this study, we focus on Rab11a protein function during hypoxia and its role in breast cancer migration. Methods: MDA-MB-468 and T47D cell lines were used in this study. Rab11a was overexpressed or suppressed by lentivirus transfection. Cobalt chloride (CoCl₂) was used to mimic a hypoxic environment. Transwell assays were performed to assess the role of Rab11a in tumor cell migration during hypoxic stimulation. The effect of hypoxia on Rab11a and epithelial-mesenchymal transition (EMT) related proteins were determined by western blot assay. Immunohistochemistry was used to determine Rab11a expression levels in breast cancer patients with axillary lymph node metastases. Results: Hypoxia-inducible factor-1α (HIF-1α) was upregulated in T47D and MDA-MB-468 cells during CoCl₂-hypoxia stimulation while Rab11a downregulation was only detected in MDA-MB-468 cells with an increased migration ability. Rab11a knockdown promoted MDA-MB-468 cells migration with a decreased E-cadherin and increased β-catenin, Vimentin and N-cadherin in hypoxic environments. In breast cancer patients, Rab11a levels were down-regulated in the metastatic axillary lymph nodes compared to the primary tumor site. Conclusions: Our study is the first to show Rab11a downregulation in triple negative breast cancer in the presence of hypoxia and raises the question of a paradoxical role of Rab11a in tumor progression.