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Metastasis is the major cause of triple‑negative breast cancer (TNBC)‑associated mortality. Hypoxia promotes cancer cell migration and remote metastasis, which occur with hypoxia inducible factor 1α (HIF‑1α) stabilization and vimentin upregulation. However, the evolutionary dynamics that link the changes in HIF‑1α and vimentin levels under hypoxic conditions are not well understood. In the present study, the effects of intermittent hypoxia (IH), continuous hypoxia (CH) and normoxia on the migration and proliferation of human TNBC MDA‑MB‑231 cells were investigated. The results demonstrated that IH significantly increased the migration of MDA‑MB‑231 cells, and this effect was dependent on the number of cycles of hypoxia‑reoxygenation. Unexpectedly, IH significantly inhibited cell proliferation, while CH only caused such an effect if hypoxia extended for ≥3 days. IH and CH induced HIF‑1α protein accumulation and vimentin upregulation, with a greater effect observed in IH. Knockdown of HIF‑1α with siRNA abolished IH‑induced cell migration and vimentin upregulation. In summary, multiple cycles of hypoxia and reoxygenation have a more pronounced effect on the promotion of TNBC invasiveness than CH; HIF‑1α activation and downstream vimentin upregulation may account for this phenotypic change. [ABSTRACT FROM AUTHOR]

Cancer/testis (CT) antigens are promising targets for immunotherapy due to their restricted expression in the germ cells of the testis in healthy tissue and high immunogenicity. The aim of the present study was to determine whether transmembrane protein 31 (TMEM31) is a CT antigen and to investigate the pattern of TMEM31 expression during the progression of melanoma. The pattern of expression of human TMEM31 mRNA in multiple human tissues was determined through reverse transcription-polymerase chain reaction analysis. TMEM31 protein expression was analyzed in the human testis, in addition to 128 primary melanoma and 64 metastatic melanoma samples through immunohistochemistry analysis. TMEM31 was identified to be predominantly expressed in the testis and weakly expressed in the placenta. In addition, TMEM31 protein expression was detected in 120/190 (63.16%) melanoma samples (primary and metastatic). The intensity of TMEM31 staining in metastatic and primary melanomas was determined through semiquantitative integrated optical density (IOD) analysis, and identified to be significantly increased in metastatic melanoma compared with primary melanoma (0.24±0.03 vs. 0.09±0.01 IOD/area; P<0.001). The expression of TMEM31 protein was significantly increased in metastatic compared with primary melanoma samples (76.56 vs. 56.35%; P=0.017). The results of the present study suggest that TMEM31 is a novel CT antigen that serves an essential role in melanoma metastasis, in addition to being a potential immunotherapeutic target for the treatment of patients with melanoma. [ABSTRACT FROM AUTHOR]