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// Li Yu 1,* , Xun Chen 2,* , Liantang Wang 1 and Shangwu Chen 3 1 Department of Pathology, The First Affiliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, P.R. China 2 Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China 3 State Key Laboratory for Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen (Zhongshan) University, Guangzhou, P.R. China * These authors have contributed equally to this work Correspondence to: Li Yu, email: // Shangwu Chen, email: // Keywords : aerobic glycolysis; Warburg effect; glucose metabolism; targets for the tumor therapy Received : November 04, 2015 Accepted : February 16, 2016 Published : February 24, 2016 Abstract Metabolic change is one of the hallmarks of tumor, which has recently attracted a great of attention. One of main metabolic characteristics of tumor cells is the high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in glycolysis pathway than that in tricarboxylic acid cycle. The molecular mechanism of a high glycolytic flux in tumor cells remains unclear. A large amount of intermediates derived from glycolytic pathway could meet the biosynthetic requirements of the proliferating cells. Hypoxia-induced HIF-1α, PI3K-Akt-mTOR signaling pathway, and many other factors, such as oncogene activation and tumor suppressor inactivation, drive cancer cells to favor glycolysis over mitochondrial oxidation. Several small molecules targeting glycolytic pathway exhibit promising anticancer activity both in vitro and in vivo . In this review, we will focus on the latest progress in the regulation of aerobic glycolysis and discuss the potential targets for the tumor therapy.

Estrogen signaling influences the development and progression of ovarian tumors, but the underlying mechanisms are not well understood. In a previous study we demonstrated that impairment of estrogen receptor alpha (ERα)-mediated olfactomedin 4 (OLFM4) expression promotes the malignant progression of endometrioid adenocarcinoma, and we identified OLFM4 as a potential target of miR-486-5p. In this study we investigated the role of OLFM4 in ovarian serous adenocarcinoma. Ovarian serous adenocarcinoma tissues had reduced OLFM4 expression. Expression of OLFM4 was positively correlated with ERα expression, and estrogen (E2) treatment in ovarian cancer cells induced OLFM4 expression in an ERα-dependent manner. In contrast to ERα, miR-486-5p levels were inversely correlated with OLFM4 expression in ovarian serous adenocarcinoma. Ovarian cancer cells transfected with miR-486-5p mimics showed decreased OLFM4 mRNA expression, and ovarian cancer cells treated with E2 showed reduced cellular miR-486-5p levels. OLFM4 knockdown enhanced proliferation, migration, and invasion by ovarian cancer cells. Low expression of OLFM4 was also associated with high tumor FIGO stage and poor tumor differentiation. These results suggest OLFM4 is downregulated by miR-486-5p, which contributes to ovarian cancer tumorigenesis. Conversely, estrogen receptor signaling downregulates miR-486-5p and upregulates OLFM4 expression, slowing the development and progression of ovarian cancer.

// Minzhi Hou 1, 3, * , Zhiqiang Cheng 2, * , Hongwei Shen 3, * , Shanyang He 3 , Yang Li 1 , Yunping Pan 4 , Chongjin Feng 4 , Xinlin Chen 5 , Yang Zhang 6 , Millicent Lin 7 , Liantang Wang 1 , Zunfu Ke 1 1 Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 2 Department of Pathology, ShenZhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, P.R. China 3 Department of Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 4 Department of Stomatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 5 Department of Preventive Medicine and Biostatistics, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China 6 Biomedical Engineering, University of Texas at El Paso, El Paso, Texas, USA 7 Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging (CIMI), California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA * These authors have contributed equally to this work Correspondence to: Zunfu Ke, e-mail: kezunfu@126.com Keywords: CTHRC1, epithelial-mesenchymal transition, epithelial ovarian cancer, β-catenin Received: May 04, 2015 Accepted: September 21, 2015 Published: October 03, 2015 ABSTRACT Collagen triple helix repeat-containing 1 (CTHRC1) is aberrantly overexpressed in multiple malignant tumors. However, the expression characteristics and function of CTHRC1 in epithelial ovarian cancer (EOC) remain unclear. We found that CTHRC1 expression was up-regulated in the paraffin-embedded EOC tissues compared to borderline or benign tumor tissues. CTHRC1 expression was positively correlated with tumor size ( p = 0.008), menopause ( p = 0.037), clinical stage ( p = 0.002) and lymph node metastasis ( p < 0.001) and was also an important prognostic factor for the overall survival of EOC patients, as revealed by Kaplan-Meier analysis. CTHRC1 increased the invasive capabilities of EOC cells in vitro by activating the Wnt/β-catenin signaling pathway. We showed that ectopic transfection of CTHRC1 in EOC cells up-regulated the expression of EMT markers such as N-cadherin and vimentin, and EMT-associated transcriptional factor Snail. Knockdown of CTHRC1 expression in EOC cells resulted in down-regulation of N-cadherin, vimentin, Snail and translocation of β-catenin. Collectively, CTHRC1 may promote EOC metastasis through the induction of EMT process and serve as a potential biomarker for prognosis as well as a target for therapy.

// Zhuo Wang 1 ,* , Chuang-Jie Cao 1 ,* , Lei-Lei Huang 1 ,* , Zun-Fu Ke 1 , Can-Jiao Luo 1 , Zhong-Wei Lin 2 , Fen Wang 1 , Yuan-Qi Zhang 3 and Lian-Tang Wang 1 1 Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 2 Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China 3 Department of Vascular Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China * These authors have contributed equally to this work Correspondence to: Lian-Tang Wang, email: // Keywords : osteosarcoma, AEG-1, EFEMP1, MMP-2, NF-κB Received : January 04, 2015 Accepted : March 03, 2014 Published : March 29, 2015 Abstract The role of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) in osteosarcoma remains unknown. Then applying EFEMP1 siRNA, plasmids transfection and adding purified EFEMP1 protein in human osteosarcoma cell lines, and using immunohistochemistry on 113 osteosarcoma tissues, demonstrated that EFEMP1 was a poor prognostic indicator of osteosarcoma; EFEMP1 was specifically upregulated in osteosarcoma and associated with invasion and metastasis in vitro and in vivo . At the same time, we found a direct regulatory effect of EFEMP1 on MMP-2. Moreover, we firstly found the marked induction of EFEMP1 by oncogenic AEG-1. And EFEMP1 expression was inhibited by the selective inhibitor of NF-κB (PDTC) in osteosarcoma cells. Then we thought that NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1. Thus, we suggested that EFEMP1 played a part as the mediator between AEG-1 and MMP-2. And NF-κB signaling pathway played an important role in this process. In summary, EFEMP1 was associated with invasion, metastasis and poor prognosis of osteosarcoma patients. EFEMP1 might indirectly enhance the expression of MMP-2, providing a potential explanation for the role of AEG-1 in metastasis. NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1.

// Zunfu Ke 1, * , Weiling He 2, * , Yuanhui Lai 3, * , Xuefeng Guo 4 , Sharon Chen 5 , Shuhua Li 1 , Yuefeng Wang 1 , Liantang Wang 1 1 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 2 Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 3 Vascular and Thyroid Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 4 Department of Gastrointestinal Surgery, the Sixth Affliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 5 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA USA * These authors contributed equally to this work. Correspondence to: Dr. Zunfu ke, e-mail: kezunfu@mail.sysu.edu.cn Dr. Liantang Wang, e-mail: wanglt@mail.sysu.edu.cn Keywords: CTHRC1 non-small cell lung cancer β-catenin metastasis prognosis Received: August 04, 2014 Accepted: August 28, 2014 Published: September 24, 2014 ABSTRACT Collagen triple helix repeat-containing 1 (CTHRC1), a novel oncogene, was identified to be aberrantly overexpressed in several malignant tumors. However, the expression profile of CTHRC1 and its clinical significance in non-small cell lung cancer (NSCLC) remain unknown. In this study, we showed that CTHRC1 was evidently overexpressed in human NSCLC tissues and NSCLC cell lines at the protein and mRNA level. Ectopic up-regulation of CTHRC1 in cancer cells resulted in elevated invasive and proliferative abilities, which were attenuated by the specific CTHRC1 siRNA. The biological effect of CTHRC1 on metastasis and proliferation was mediated by the activation of the Wnt/β-catenin pathway. Furthermore, CTHRC1 immunoreactivity was evidently overexpressed in paraffin-embedded NSCLC tissues (212/292, 72.60%) in comparison to corresponding adjacent non-cancerous tissues (6/66, 9.09%) ( p