Autotaxin exacerbates tumor progression by enhancing MEK1 and overriding the function of miR-489-3p
Upregulated expression of autotaxin, a secreted phospholipase and phosphodiesterase enzyme, appears in malignant disease. The identification of a circulating miRNA signature should distinguish autotaxin-mediated disease and also elucidate unknown molecular mechanisms that rationalize its malignant potential. Using female transgenic ‘AT-ATX’ mice, whereby human wild-type autotaxin is expressed in liver under the control of the alpha-1 antitrypsin promoter, transgenic animals express augmented autotaxin in circulation and a percentage develop tumors. (Source: Cancer Letters)
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Sudeepti S. Kuppa, Wei Jia, Shuying Liu, Ha Nguyen, Susan S. Smyth, Gordon B. Mills, Kevin K. Dobbin, William J. Hardman, Mandi M. Murph Tags: Original Articles Source Type: research
Overexpression of MIST1 reverses the epithelial-mesenchymal transition and reduces the tumorigenicity of pancreatic cancer cells via the Snail/E-cadherin pathway
The role of transcription factors in cancer has attracted significant attention. Although genetic models indicate MIST1 functions as a tumor suppressor in mice, its role in human pancreatic cancer is unclear. We explored the expression and function of MIST1 in pancreatic cancer. Analysis of three GEO datasets (GSE16515, GSE15471, and GSE62165) showed MIST1 mRNA was significantly downregulated in human pancreatic cancer compared to normal pancreatic tissues. Moreover, MIST1 protein and mRNA expression were downregulated in pancreatic cancer cell lines compared to normal cells. (Source: Cancer Letters)
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Xiaogang Li, Hengyu Chen, Zhiqiang Liu, Zeng Ye, Shanmiao Gou, Chunyou Wang Tags: Original Articles Source Type: research
Targeting autophagy enhances apatinib-induced apoptosis via endoplasmic reticulum stress for human colorectal cancer
Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma and some other solid tumors. However, the direct functional mechanisms of tumor lethality mediated by apatinib have not yet been fully characterized, and the precise mechanisms of drug resistance are largely unknown. Here, in this study, we demonstrated that apatinib could induce both apoptosis and autophagy in human colorectal cancer (CRC) via a mechanism that involved endoplasmic reticulum (ER) stress. (Source: Cancer Letters)
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Xi Cheng, Haoran Feng, Haoxuan Wu, Zhijian Jin, Xiaonan Shen, Jie Kuang, Zhen Huo, Xianze Chen, Haoji Gao, Feng Ye, Xiaopin Ji, Xiaoqian Jing, Yaqi Zhang, Tao Zhang, Weihua Qiu, Ren Zhao Tags: Original Articles Source Type: research
The hypoxic tumor microenvironment in vivo selects the tumor cells with increased survival against genotoxic stresses
Tumor sensitivity to radiation therapy has been known to be dependent on O2 concentrations. However, radiosensitivity of naturally occurring hypoxic tumor cells remains to be well fully investigated in direct comparison to that of their adjacent non-hypoxic tumor cells within the same tumor. We developed a hypoxia-sensing xenograft model using the hypoxia-response element (HRE)-driven enhanced green fluorescence protein (EGFP) as a hypoxia reporter to identify hypoxic tumor cells in situ. Here, we have found that naturally hypoxic tumor cells are moderately radioresistant compared to their neighboring non-hypoxic tumor cel...
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Hoon Kim, Qun Lin, Zhong Yun Tags: Original Articles Source Type: research
Piribedil disrupts the MLL1-WDR5 interaction and sensitizes MLL-rearranged acute myeloid leukemia (AML) to doxorubicin-induced apoptosis
Targeting WT MLL for the treatment of MLL-r leukemia, which is highly aggressive and resistant to chemotherapy, has been shown to be a promising strategy. However, drug treatments targeting WT MLL are lacking. We used an in vitro histone methyltransferase assay to screen a library consists of 592 FDA –approved drugs for MLL1 inhibitors by measuring alterations in HTRF signal and found that Piribedil represented a potent activity. Piribedil specifically inhibited the proliferation of MLL-r cells by inducing cell-cycle arrest, apoptosis and myeloid differentiation with little toxicity to the non -MLL cells. (Source: Cancer Letters)
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Xiong Zhang, Xingling Zheng, Hong Yang, Juan Yan, Xuhong Fu, Rongrui Wei, Xiaowei Xu, Zhuqing Zhang, Aisong Yu, Kaixin Zhou, Jian Ding, Meiyu Geng, Xun Huang Tags: Original Articles Source Type: research
Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model
Aberrant reactions of signal transducer and transcriptional activator (STAT) are frequently detected in multiple myeloma (MM) cancers and can upregulate the expression of multiple genes related to cell proliferation, survival, metastasis, and angiogenesis. Therefore, agents capable of inhibiting STAT activation can form the basis of novel therapies for MM patients. In the present study, we investigated whether the potential anti-cancer effects of Formononetin (FT), a naturally occurring isoflavone derived from Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, against MM cell lines and hu...
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Chulwon Kim, Seok-Geun Lee, Woong Mo Yang, Frank Arfuso, Jae-Young Um, Alan Prem Kumar, Jinsong Bian, Gautam Sethi, Kwang Seok Ahn Tags: Original Articles Source Type: research
Insight into the Roles of Vitamins C and D against Cancer: Myth or Truth?
The consumption of vitamins C and D for prevention and treatment of cancer is still an uncertain recommendation due to their controversial roles in cancer. The epidemiological studies document that vitamins C and D possess potential antineoplastic property. In addition, accumulating experimental studies strongly support their anticancer efficacy both in vitro and in vivo, although the mechanisms of action are not completely clear. Vitamin C at pharmacological concentration has cancer-selective cytotoxicity in several cancer cell lines. (Source: Cancer Letters)
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Cai-Ning Zhao, Ya Li, Xiao Meng, Sha Li, Qing Liu, Guo-Yi Tang, Ren-You Gan, Hua-Bin Li Tags: Mini-review Source Type: research
New insights into the biological impacts of immune cell-derived exosomes within the tumor environment
Exosomes are a group of nano-sized membrane vesicles that transfer proteins, nucleic acids, and lipids to nearby and faraway cells, playing an important role in the intercellular communication within the extracellular environment. Emerging evidences show that exosomes derived from immunocytes, including dendritic cells, T cells, B cells, macrophages, natural killer cells and myeloid-derived suppressor cells, can play an intimate role in the crosstalk among immunocytes in a tumor microenvironment. (Source: Cancer Letters)
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Meng Shen, Xiubao Ren Tags: Mini-review Source Type: research
Pinocembrin induces ER stress mediated apoptosis and suppresses autophagy in melanoma cells
Melanoma, one of the toughest tumors to treat, features high metastasis and high lethality. Pinocembrin is a natural flavanone with versatile biological and pharmacological activities. Here, we evaluated the anti-tumor effects of pinocembrin against melanoma in vitro and in vivo. In vitro, pinocembrin inhibited the proliferation of melanoma cells (B16F10 and A375) in a dose-dependent manner. It induced endoplasmic reticulum stress via IRE1 α/Xbp1 pathway and triggered caspase-12/-4 mediated apoptosis in both cell lines. (Source: Cancer Letters)
Source: Cancer Letters - May 26, 2018 Category: Cancer & Oncology Authors: Yufei Zheng, Kai Wang, Yuqi Wu, Yifan Chen, Xi Chen, Chenyue W. Hu, Fuliang Hu Tags: Original Articles Source Type: research
Sulforaphane-N-Acetyl-Cysteine inhibited autophagy leading to apoptosis via Hsp70-mediated microtubule disruption
Sulforaphane-N-acetyl-cysteine (SFN-NAC) is a potential drug to inhibit human non-small cell lung cancer (NSCLC), but the underlying mechanisms are elusive. Here, we uncovered that SFN-NAC induced apoptosis via flow cytometer assay and transmission electron microscopy. Further, SFN-NAC increased LC3 II/LC3 I and the number of LC3 punctas, but Western blot showed that SFN-NAC inhibited cell autophagy in response to a co-treatment of Bafilomycin A1 and SFN-NAC. Furthermore, immunofluorescence staining and Western blot showed that SFN-NAC triggered microtubule disruption causing apoptosis via downregulating α-tubulin and pho...
Source: Cancer Letters - May 26, 2018 Category: Cancer & Oncology Authors: Yabin Hu, Yan Zhou, Gaoxiang Yang, Yalin Wang, Zhongnan Zheng, Juntao Li, Yuting Yan, Wei Wu Tags: Original Articles Source Type: research
Comprehensive pharmacogenomic profiling of human papillomavirus-positive and -negative squamous cell carcinoma identifies sensitivity to aurora kinase inhibition in KMT2D mutants
To address the unmet need for effective biomarker-driven targeted therapy for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) and cervical cancer, we conducted a high-throughput drug screen using 1122 compounds in 13 HPV-positive and 11 matched HPV-negative cell lines. The most effective drug classes were inhibitors of polo-like kinase, proteasomes, histone deacetylase, and Aurora kinases. Treatment with a pan-Aurora inhibitor, danusertib, led to G2M arrest and apoptosis in vitro. (Source: Cancer Letters)
Source: Cancer Letters - May 25, 2018 Category: Cancer & Oncology Authors: Nene N. Kalu, Tuhina Mazumdar, Shaohua Peng, Pan Tong, Li Shen, Jing Wang, Upasana Banerjee, Jeffrey N. Myers, Curtis R. Pickering, David Brunell, Clifford C. Stephan, Faye M. Johnson Tags: Original Articles Source Type: research
Curcumin suppresses oncogenicity of human colon cancer cells by covalently modifying the cysteine 67 residue of SIRT1
SIRT1, an NAD+-dependent histone/protein deacetylase, has diverse physiological actions. Recent studies have demonstrated that SIRT1 is overexpressed in colorectal cancer, suggesting its oncogenic potential. However, the molecular mechanisms by which overexpressed SIRT1 induces the progression of colorectal cancer and its inhibition remain largely unknown. Curcumin (diferuloymethane), a major component of the spice turmeric derived from the plant Curcuma longa L., has been reported to exert chemopreventive and anti-carcinogenic effects on colon carcinogenesis. (Source: Cancer Letters)
Source: Cancer Letters - May 25, 2018 Category: Cancer & Oncology Authors: Yeon-Hwa Lee, Na-Young Song, Jinyoung Suh, Do-Hee Kim, Wonki Kim, Jihyae Ann, Jeewoo Lee, Jeong-Heum Baek, Hye-Kyung Na, Young-Joon Surh Tags: Original Articles Source Type: research
miRNAs in immune responses to Mycobacterium tuberculosis infection
Tuberculosis (TB) is one of the most fatal infectious diseases, affecting one third of the world's population. The causative agent, Mycobacterium tuberculosis (Mtb), has a well-established ability to circumvent the host's immune system for its long-term intracellular survival. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune response. They act by negatively regulating the expression levels of important genes in both innate and adaptive immunity. It has been established in recent studies that the host immune response against Mtb is regulated by many miRNAs, most of which are induced by Mtb infection....
Source: Cancer Letters - May 24, 2018 Category: Cancer & Oncology Authors: Tianshu Yang, Baoxue Ge Tags: Mini-review Source Type: research
Nemo-Like Kinase (NLK) Primes Colorectal Cancer Progression by Releasing the E2F1 Complex from HDAC1
Control of E2F1 activity is restricted via its interactions with RB1 and HDAC1. However, the detailed regulatory mechanisms underlying the E2F1/HDAC1 complex remain elusive. Here, we report that nemo-like kinase (NLK) boosts cell cycle progression, which facilitates tumor development by releasing the E2F1 protein from HDAC1. Deletion of NLK largely blocks colorectal tumor proliferation and development. Moreover, RNA-seq shows that cell cycle is arrested at the G1/S phase in NLK-deficient cells and that the expression of E2F complex-targeted genes is affected, whereas overexpression of NLK but not an NLK mutant restores the...
Source: Cancer Letters - May 24, 2018 Category: Cancer & Oncology Authors: Shang-Ze Li, Feng Zeng, Jun Li, Qi-Peng Shu, Hui-Hui Zhang, Jun Xu, Jian-Wei Ren, Xiao-Dong Zhang, Xue-Min Song, Run-Lei Du Tags: Original Articles Source Type: research
CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis
As a class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified to regulate tumourigenesis and progression in multiple malignancies. However, the expression profiles and function of circRNAs in breast cancer metastasis are largely unknown. Here, we determined that the expression of a novel circRNA, which we named circIRAK3, was increased in metastatic breast cancer (BC) cells and predictive of BC recurrence. Gain-of-function and loss-of-function studies in BC cells demonstrated that circIRAK3 promoted cell migration, invasion and metastasis in vitro and in vivo but did not affect cell prolif...
Source: Cancer Letters - May 24, 2018 Category: Cancer & Oncology Authors: Jie Wu, Zerun Jiang, Chen Chen, Qingsong Hu, Ziyi Fu, Junjie Chen, Zhangding Wang, Qiang Wang, Aiping Li, Jeffrey R. Marks, Changying Guo, Yun Chen, Jianwei Zhou, Liuqing Yang, Chunru Lin, Shouyu Wang Tags: Original Articles Source Type: research
