Qin J.-J.,Texas Tech University Health Sciences Center |
Nag S.,Texas Tech University Health Sciences Center |
Wang W.,Texas Tech University Health Sciences Center |
Zhou J.,Nanjing Medical University |
And 4 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2014
The NFAT signaling pathway regulates various aspects of cellular functions; NFAT acts as a calcium sensor, integrating calcium signaling with other pathways involved in development and growth, immune response, and inflammatory response. The NFAT family of transcription factors regulates diverse cellular functions such as cell survival, proliferation, migration, invasion, and angiogenesis. The NFAT isoforms are constitutively activated and overexpressed in several cancer types wherein they transactivate downstream targets that play important roles in cancer development and progression. Though the NFAT family has been conclusively proved to be pivotal in cancer progression, the different isoforms play distinct roles in different cellular contexts. In this review, our discussion is focused on the mechanisms that drive the activation of various NFAT isoforms in cancer. Additionally, we analyze the potential of NFAT as a valid target for cancer prevention and therapy. © 2014 Elsevier B.V. Source
Chen P.,University of Chinese Academy of Sciences |
Li C.,University of Chinese Academy of Sciences |
Li X.,University of Chinese Academy of Sciences |
Li J.,University of Chinese Academy of Sciences |
And 4 more authors.
British Journal of Cancer | Year: 2014
Background: Many epidemiological studies have investigated the association between folate intake, circulating folate level and risk of breast cancer; however, the findings were inconsistent between the studies. Methods: We searched the PubMed and MEDLINE databases updated to January, 2014 and performed the systematic review and meta-analysis of the published epidemiological studies to assess the associations between folate intake level, circulating folate level and the overall risk of breast cancer. Results: In all, 16 eligible prospective studies with a total of 744 068 participants and 26 205 breast cancer patients and 26 case-control studies with a total of 16 826 cases and 21 820 controls that have evaluated the association between folate intake and breast cancer risk were identified. Pooled analysis of the prospective studies and case-control studies suggested a potential nonlinearity relationship for dietary folate intake and breast cancer risk. Prospective studies indicated a U-shaped relationship for the dietary folate intake and breast cancer risk. Women with daily dietary folate intake between 153 and 400 μg showed a significant reduced breast cancer risk compared with those <153 μg, but not for those >400 μg. The case-control studies also suggested a significantly negative correlation between the dietary folate intake level and the breast cancer risk. Increased dietary folate intake reduced breast cancer risk for women with higher alcohol intake level, but not for those with lower alcohol intake. No significant association between circulating folate level and breast cancer risk was found when the results of 8 identified studies with 5924 participants were pooled. Conclusions: Our studies suggested that folate may have preventive effects against breast cancer risk, especially for those with higher alcohol consumption level; however, the dose and timing are critical and more studies are warranted to further elucidate the questions.© 2014 Cancer Research UK. All rights reserved. Source
Sun H.,Chinese Academy of Sciences |
Li X.,Chinese Academy of Sciences |
Fan L.,Chinese Academy of Sciences |
Wu G.,Fudan University |
And 3 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2014
TNF receptor associated factor 6 (TRAF6) plays a critical role in the regulation of innate immune responses and adaptive immune responses. Though recent studies indicate that TRAF6 is involved in cancer, its precise role in cancer including colon cancer has not been extensively investigated and remains largely unknown. The purpose of this work is to determine the expression of TRAF6 in colon cancer as well as the possible role of it in proliferation and apoptosis of colon cancer cells. Fifty colon cancer tissues paired with their adjacent non-cancerous tissues were analyzed. TRAF6 expression is upregulated in cancers (P = 0.000), which is correlated with tumor grades (P = 0.012). The tumor tissue-array analysis also indicates that expression of TRAF6 is upregulated in colon cancer (P = 0.000), but the TRAF6 upregulation has no association with patients' survival rate (P = 0.055). We found that knockdown of TRAF6 blocks proliferation of colon cancer cells through cyclin D1. Different from other reports, in our experiments knockdown of TRAF6 alone has little effect on survival of colon cancer cells examined. Knockdown of TRAF6 sensitizes the cells to treatment of the conventional anti-cancer drugs 5-fluorouracil and etoposide. Thus, inhibition of TRAF6 may improve the therapeutic treatment of these drugs. Together, our data suggest that TRAF6 promotes proliferation of colon cancer cells and it may serve as a potential target for therapy of colon cancer. © 2014 Elsevier Ltd. Source
Zhang Y.,Shanghai University |
Guan D.-X.,CAS Shanghai Institutes for Biological Sciences |
Shi J.,Shanghai University |
Gao H.,CAS Shanghai Institutes for Biological Sciences |
And 13 more authors.
Journal of Hepatology | Year: 2013
Background & Aims Systemic chemotherapy serves as an adjuvant treatment for post-operation patients with hepatocellular carcinoma (HCC), and provides curative option for the patients with unresectable HCC. However, its efficiency is largely limited because of the high incidence of chemo-resistance. Increasing evidence has shown that tumor initiating cells (TICs) not only have the ability to self-renew and drive the initiation and progression of cancer, but also exhibit greater resistance to conventional chemo- and radio-therapies than non-TICs. It was the aim of this study to investigate the effects of ATRA with and without cisplatin on TIC differentiation and apoptosis in human HCC. Methods In the present study, we evaluated the TICs of HCC cell differentiation induced by all-trans retinoic acid (ATRA), and developed a novel chemotherapeutic approach to HCC, by characterizing the function of combinatorial treatment with cis-diammineplatinum(II) (cisplatin) and ATRA in vitro and in vivo. Results ATRA effectively induced differentiation of TICs, which potentiated the cytotoxic effects of cisplatin. The combinatorial treatment of ATRA acid and cisplatin reduced protein kinase B (AKT) (Thr308) phosphorylation, and promoted apoptosis of HCC cells more significantly than treatment with cisplatin alone. In addition, the combined treatment with the two drugs exerted stronger inhibition on either HCC cell migration in vitro or metastasis in vivo, when compared to the treatment with either drug alone. Conclusions These results indicated that ATRA could significantly improve the effect of cisplatin, which is at least partially attributed to ATRA-induced differentiation of HCC TICs, and the subsequent decrease in this chemo-resistant subpopulation. © 2013 European Association for the Study of the Liver. Published. Source
Guo J.,CAS Shanghai Institutes for Biological Sciences |
Xu Y.,CAS Shanghai Institutes for Biological Sciences |
Ji W.,CAS Shanghai Institutes for Biological Sciences |
Song L.,CAS Shanghai Institutes for Biological Sciences |
And 3 more authors.
Toxicology Letters | Year: 2015
Metastasis is the leading cause of deaths in patients with breast cancer. Benzo[a]pyrene is a cumulative carcinogen and ubiquitous environmental pollutant with potent carcinogenic properties. As we report here, we established an accumulative mouse model mimicking the cumulative effects of benzo[a]pyrene exposure in human breast carcinogenesis. Our focus was on elucidating the mechanisms by which benzo[a]pyrene contributes to the process of breast cancer metastasis. Our study indicated that benzo[a]pyrene increased the migration of breast cancer cells both in vitro and in vivo. Specifically, we demonstrated that benzo[a]pyrene enhances breast cancer cell migration and invasion by up-regulating ROS-induced ERK signaling, leading to the activation of matrix metalloproteinases 9. Our results suggest that benzo[a]pyrene-induced mammary gland cancer metastasis is an important and intricate process facilitated by cumulative benzo[a]pyrene exposure leading to activation of the ROS-ERK-MMP9 signaling pathway. © 2015 Elsevier Ireland Ltd. Source