The treatment of BLBC represents an unmet medical need. Wu et al. show that AKR1B1 facilitates BLBC progression through a positive feedback loop that activates the EMT program, suggesting that inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC.

receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer. Core tip: Breast cancer cells display distinct metabolic characteristics according to different molecular phe notypes. There may be crosstalk with the estrogen receptor and human epidermal growth factor receptor2 signal pathways in the metabolic regulation in breast cancer cells that make it more complex to evaluate the efficiency of an antimetabolic drug. On the other hand, the research on target metabolism in breast cancer will also largely help us to understand the complicated mechanism by which an antimetabolic drug impro ves the efficacy of cancer therapy or overcomes drug resistance. AbstractAdjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor MINIREVIEWS 122February 10, 2016|Volume 7|Issue 1|

Mounting evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated and implicated in the occurrence and development of a wide range of human malignancies. LINC00461, a novel cancer‐related lncRNA, has been reported to be highly expressed and serve as oncogene in glioma; however, its biological role in breast cancer (BC) remains obscure. This study aimed to explore the role of LINC00461 in BC and elucidate the potential molecular mechanisms involved. In the current study, LINC00461 was found to be significantly upregulated in both BC tissues and cell lines. Besides, we found that high LINC00461 expression was associated with TNM stage and differentiation. Furthermore, functional studies demonstrated that LINC00461 expedited BC cell migration and invasion. Notably, LINC00461 was observed to enhance the expression of vimentin and zinc‐finger E‐box binding homeobox factor 1, suppress the expression of E‐cadherin, and promote the activation of extracellular signal‐regulated kinase and AKT signaling pathways. Mechanical investigations revealed that LINC00461 positively modulated integrin β3 (ITGB3) expression as miR‐30a‐5p sponge in BC cells. Taken together, LINC00461 exerts an oncogenic role in BC through miR‐30a‐5p/ITGB3 axis. Our data indicate that LINC00461 may be used to be a novel candidate therapeutic target and a valuable diagnostic biomarker for BC.

Previous studies have reported that vitexins induce cytotoxic effects. In the present study, we investigate a new native lignan vitexin 6 (VB6) in vitro to determine the molecular mechanism underlying its cytotoxicity. We screened and cultured several tumor cell lines and subsequently analyzed VB6 cytotoxicity against 14 different tumor cell lines using a 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The expression of proteins that regulate apoptosis and autophagy was determined using western blot analysis. VB6 showed an excellent cytotoxic effect against various cancer cell lines in vitro. It induced apoptosis and autophagy of cancer cells. VB6-induced apoptosis showed a time-dependent and concentration-dependent relationship with cleaved poly (ADP-ribose) polymerase, cleaved caspase-3, Bax upregulation, and Bcl-2 downregulation. The levels of Beclin-1 and LC3-II, which are markers for cell autophagy, gradually increased after VB6 treatment. Jun N-terminal kinase (JNK) phosphorylation was increased after VB6 treatment, accompanied by upregulation of P-Bcl-2 and P-C-Jun expression. Cotreatment with a JNK inhibitor significantly decreased VB6-induced cell death and downregulated P-Bcl-2, and cleaved PARP and Beclin-1 expression. The new native lignan VB6 inhibits cancer cell proliferation by activating the JNK pathway. We believe that VB6 could be a valuable chemotherapeutic drug after further evaluation.

MicroRNAs (miRNAs) are associated with the formation and progression of many types of cancers. In the present study, the aim was to elucidate the involvement of miR-146a-5p in the regulation of human breast cancer (BC) cell growth and invasion, as well as the mechanisms underlying its effects. Reverse transcription-quantitative polymerase chain reaction results revealed that miR-146a-5p was markedly downregulated in BC tissues relative to those of adjacent normal tissues. miR-146a-5p expression was also markedly downregulated in BC cells. Overexpression of miR-146a-5p significantly suppressed the proliferation, invasion and migration of BC MDA-MB-453 and MCF7 cells. Furthermore, the results indicated that miR-146a-5p downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) by directly binding to its 3′-untranslated region in BC cells. Furthermore, IRAK1 expression was observed to be markedly upregulated and inversely correlated with miR-146a-5p expression in BC tissues. Mechanical studies indicated that restoring IRAK1 expression reversed the miR-146a-5p-induced inhibitory effects on proliferation and invasion of BC cells. In conclusion, miR-146a-5p may act as a tumor suppressor in BC by directly targeting IRAK1. These results highlighted the potential of miR-146a-5p as a novel therapeutic target for the treatment of BC.