Aldolase A (ALDOA) is one of the glycolytic enzymes primarily found in the developing embryo and adult muscle. Recently, a new role of ALDOA in several cancers has been proposed. However, the underlying mechanism remains obscure and inconsistent. In this study, we tried to investigate ALDOA-associated (AA) genes using available microarray datasets to help elucidating the role of ALDOA in cancer. In the dataset of patients with non-small-cell lung cancer (NSCLC, E-GEOD-19188), 3448 differentially expressed genes (DEGs) including ALDOA were identified, in which 710 AA genes were found to be positively associated with ALDOA. Then according to correlation coefficients between each pair of AA genes, ALDOA-associated gene co-expression network (GCN) was constructed including 182 nodes and 1619 edges. 11 clusters out of GCN were detected by ClusterOne plugin in Cytoscape, and only 3 of them have more than three nodes. These three clusters were functionally enriched. A great number of genes (43/79, 54.4%) in the biggest cluster (Cluster 1) primarily involved in biological process like cell cycle process (P a = 6.76E-26), mitotic cell cycle (P a = 4.09E-19), DNA repair (P a = 1.13E-04), M phase of meiotic cell cycle (P a = 0.006), positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle (P a = 0.014). AA genes with highest degree and betweenness were considered as hub genes of GCN, namely CDC20, MELK, PTTG1, CCNB2, CDC45, CCNB1, TK1 and PSMB2, which could distinguish cancer from normal controls with ALDOA. Their positive association with ALDOA remained after removing the effect of HK2 and PKM, the two rate limiting enzymes in glycolysis. Further, knocking down ALDOA blocked breast cancer cells in the G0/G1 phase under minimized glycolysis. All suggested that ALDOA might affect cell cycle progression independent of glycolysis. RT-qPCR detection confirmed the relationship of ALDOA with CDC45 and CCNB2 in breast tumors. High expression of the hub genes indicated poor outcome in NSCLC. ALDOA could improve their predictive power. ALDOA could contribute to the progress of cancer, at least partially through its association with genes relevant to cell cycle independent of glycolysis. AA genes plus ALDOA represent a potential new signature for development and prognosis in several cancers.

The transcription factor forkhead box C1 (FOXC1) has recently been proposed as a crucial regulator triple‐negative breast cancer (TNBC) and associated with TNBC metastasis. However, the mechanism of FOXC1 function in TNBC development and metastasis was elusive. In this study, overexpression of FOXC1 in MDA‐MB‐231 cells significantly enhanced, while knockdown of FOXC1 in BT549 cells significantly reduced the capabilities of TNBC cell invasion and motility in vitro and metastasis to the lung in vivo, when compared to their respective control cells. Mechanistic studies revealed that FOXC1 increased the expression of chemokine receptor‐4 (CXCR4), probably through transcriptional activation. AMD3100, an inhibitor of CXCR4, could block cell migration. In zebrafish tumor model, AMD3100 could suppress cell invasion and metastasis. In addition, overexpressing CXCR4 in FOXC1‐knockdown BT549 cells increased the capabilities of TNBC cell invasion and motility. In contrast, inhibition of CXCR4 with either AMD3100 or siRNA in MDA‐MB‐231 cells overexpressing FOXC1 reduced the capabilities of invasion and motility. Taken together, our results may reveal potential mechanism for FOXC1‐induced TNBC metastasis.

Targeting fatty acid synthase sensitizes human nasopharyngeal carcinoma cells to radiation via downregulating frizzled class receptor 10

The RAS-RAF-MEK-ERK signaling pathway (MAPK signaling pathway) plays a significant role in multiple pathological behaviors and is most frequently dysregulated in more than 30% of human cancers. As key elements in this pathway, MEK1/2 play crucial roles in tumorigenesis and the inhibition of apoptosis, which makes their inhibition an attractive antitumor strategy. Dozens of potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed that have produced substantial improvement in clinical outcomes over the past decade. However, the efficacy of these agents is limited, and response rates are variable in a wide range of tumors that harbor RAS and RAF mutations due to the development of resistance, which is derived mainly from the persistence of MAPK signaling and increased activation of the mutual feedback networks. Both intrinsic and acquired resistance to MEK inhibitors necessitates the synergistic targeting of both pathways to restore the therapeutic effects of a single agent. In this review, the significant role of the MAPK pathway in carcinogenesis and its therapeutic potential are comprehensively examined with a focus on MEK inhibitors. Then, the activation of feedback networks accompanying MEK inhibition is briefly reviewed. Combination strategies that involve the simultaneous inhibition of the original and resistance pathways are highlighted and elaborately described on the basis of the latest research progress. Finally, the obstacles to the development of MEK-related combination systems are discussed in order to lay the groundwork for their clinical application as frontline treatments for individual patients with MAPK-hyperactivated malignancies.

The detection of circulating tumor cells (CTCs) still faces a huge challenge partially because of low abundance of CTCs (1-10 cells/mL). In this work, a plasmonic titled fiber Bragg grating biosensor is proposed for detection of breast cancer cells. The biosensor is made by an 18° TFBG with a 50 nm-thick gold nanofilm coating over the surface of the fiber, further immobilized with a specific antibody against GPR30, which is a membrane receptor expressed in many breast cancers, serving as bait. In vitro tests have confirmed that the proposed biosensor can detect breast cancer cells in concentration of 5 cells/mL within 20 minutes and has good linearity in the range of 5–1000 cells/mL, which has met the requirement of CTC detection in real conditions. Furthermore, theoretical analysis based on the experimental results shows that the limit of detection can even reach single-cell level. Our proposed biosensor has a simple structure, is easy to manufacture, is of small size, and has a good performance, making it a good choice for real-time, label-free, and milliliter-volume detection of cancer cells in future.

Chromosome 1 open reading frame 63 (C1orf63) is located on the distal short arm of chromosome 1, whose allelic loss has been observed in several human cancers. C1orf63 has been reported to be up-regulated in IL-2-starved T lymphocytes, which suggests it might be involved in cell cycle control, a common mechanism for carcinogenesis. Here we investigated the expression and clinical implication of C1orf63 in breast cancer. Paraffin-embedded specimens, clinicopathological features and follow-up data of the breast cancer patients were collected. Publicly available microarray and RNA-seq datasets used in this study were downloaded from ArrayExpress of EBI and GEO of NCBI. KM plotter tool was also adopted. The expression of C1orf63 and CDK10, one known cell cycle-dependent tumor suppressor in breast cancer, was assessed by immunohistochemistry. Western blotting was performed to detect C1orf63 protein in human breast cancer cell lines, purchased from the Culture Collection of the Chinese Academy of Sciences, Shanghai. In a group of 12 human breast tumors and their matched adjacent non-cancerous tissues, C1orf63 expression was observed in 7 of the 12 breast tumors, but not in the 12 adjacent non-cancerous tissues (P < 0.001). Similar results were observed of C1orf63 mRNA expression both in breast cancer and several other cancers, including lung cancer, prostate cancer and hepatocellular carcinoma. In another group of 182 breast cancer patients, C1orf63 expression in tumors was not correlated with any clinicopathological features collected in this study. Survival analyses showed that there was no significant difference of overall survival (OS) rates between the C1orf63 (+) group and the C1orf63 (−) group (P = 0.145). However, the analyses of KM plotter displayed a valid relationship between C1orf63 and RFS (relapse free survival)/OS (P < 0.001; P = 0.007). Notablely, in breast cancers with advanced TNM stages (III ~ IV) among these 182 patients, C1orf63 expression was an independent prognostic factor predicting better clinical outcome (HR: 0.41; 95 % CI: 0.17 ~ 0.97; P = 0.042). Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r_s = 0.391; P < 0.001). Compared to adjacent non-cancerous tissues, C1orf63 expression was elevated in tumor tissues. However, C1orf63 predicts better prognosis for breast cancers with advanced TNM stage, and the underlying mechanism is unknown. In addition, C1orf63 is correlated with the cell cycle related gene, CDK10.