Improving Fascin Inhibitors to Block Tumor Cell Migration and Metastasis
Tumor metastasis is the major cause of mortality of cancer patients, being responsible for ∼90% of all cancer deaths. One of the key steps during tumor metastasis is tumor cell migration which requires actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are antenna-like filopodia. Fascin protein is the main actin-bundling protein in filopodia. Here we report the development of fascin-specific small-molecules that inhibit the interaction between fascin and actin. (Source: Molecular Oncology)
Source: Molecular Oncology - March 31, 2016 Category: Cancer & Oncology Authors: Shaoqin Han, Jianyun Huang, Bingqian Liu, Bowen Xing, Francois Bordeleau, Cynthia A. Reinhart-King, Wenxin Li, J. Jillian Zhang, Xin-Yun Huang Source Type: research
Combination therapy induces unfolded protein response and cytoskeletal rearrangement leading to mitochondrial apoptosis in prostate cancer
Development of therapeutic resistance is responsible for most prostate cancer (PCa) related mortality. Resistance has been attributed to an acquired or selected cancer stem cell phenotype. Here we report the histone deacetylase inhibitor apicidin (APC) or ER stressor thapsigargin (TG) potentiate paclitaxel (TXL)-induced apoptosis in PCa cells and limit accumulation of cancer stem cells. TXL-induced responses were modulated in the presence of TG with increased accumulation of cells at G1-phase, rearrangement of the cytoskeleton, and changes in cytokine release. (Source: Molecular Oncology)
Source: Molecular Oncology - March 30, 2016 Category: Cancer & Oncology Authors: Sandeep Kumar, Ajay K. Chaudhary, Rahul Kumar, Jordan O'Malley, Anna Dubrovska, Xinjiang Wang, Neelu Yadav, David W. Goodrich, Dhyan Chandra Source Type: research
Combination therapy induces unfolded protein response and cytoskeletal rearrangement leading to mitochondrial apoptosis in prostate cancer
Development of therapeutic resistance is responsible for most prostate cancer (PCa) related mortality. Resistance has been attributed to an acquired or selected cancer stem cell phenotype. Here we report the histone deacetylase inhibitor apicidin (APC) or ER stressor thapsigargin (TG) potentiate paclitaxel (TXL)-induced apoptosis in PCa cells and limit accumulation of cancer stem cells. TXL-induced responses were modulated in the presence of TG with increased accumulation of cells at G1-phase, rearrangement of the cytoskeleton, and changes in cytokine release. (Source: Molecular Oncology)
Source: Molecular Oncology - March 30, 2016 Category: Cancer & Oncology Authors: Sandeep Kumar, Ajay K. Chaudhary, Rahul Kumar, Jordan O'Malley, Anna Dubrovska, Xinjiang Wang, Neelu Yadav, David W. Goodrich, Dhyan Chandra Source Type: research
Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody
The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). (Sourc...
Source: Molecular Oncology - March 27, 2016 Category: Cancer & Oncology Authors: Simona Cignetto, Chiara Modica, Cristina Chiriaco, Lara Fontani, Paola Milla, Paolo Michieli, Paolo M. Comoglio, Elisa Vigna Source Type: research
Dual Constant Domain-Fab: a novel strategy to improve half-life and potency of a Met therapeutic antibody
The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). (Sourc...
Source: Molecular Oncology - March 27, 2016 Category: Cancer & Oncology Authors: Simona Cignetto, Chiara Modica, Cristina Chiriaco, Lara Fontani, Paola Milla, Paolo Michieli, Paolo M. Comoglio, Elisa Vigna Source Type: research
Unbiased identification of substrates of protein tyrosine phosphatase ptp-3 in C. elegans
The leukocyte antigen related (LAR) family of receptor-like protein tyrosine phosphatases has three members in humans – PTPRF, PTPRD and PTPRS – that have been implicated in diverse processes including embryonic development, inhibition of cell growth and axonal guidance. Mutations in the LAR family are associated with developmental defects such as cleft palate as well as various cancers including breast, neck, lung, colon and brain. Although this family of tyrosine phosphatases is important for many developmental processes, little is known of their substrates. (Source: Molecular Oncology)
Source: Molecular Oncology - March 24, 2016 Category: Cancer & Oncology Authors: Christopher J. Mitchell, Min-Sik Kim, Jun Zhong, Raja Sekhar Nirujogi, Anjun K. Bose, Akhilesh Pandey Source Type: research
Unbiased identification of substrates of protein tyrosine phosphatase ptp-3 in C. elegans
The leukocyte antigen related (LAR) family of receptor-like protein tyrosine phosphatases has three members in humans – PTPRF, PTPRD and PTPRS – that have been implicated in diverse processes including embryonic development, inhibition of cell growth and axonal guidance. Mutations in the LAR family are associated with developmental defects such as cleft palate as well as various cancers including breast, neck, lung, colon and brain. Although this family of tyrosine phosphatases are important for many developmental processes, little is known of their substrates. (Source: Molecular Oncology)
Source: Molecular Oncology - March 24, 2016 Category: Cancer & Oncology Authors: Christopher J. Mitchell, Min-Sik Kim, Jun Zhong, Raja Sekhar Nirujogi, Anjun K. Bose, Akhilesh Pandey Source Type: research
Novel sesquiterpene lactone analogues as potent anti-breast cancer agents
In this study, fifty-eight ester derivatives (DETDs) with a novel sesquiterpene dilactone skeleton were organically synthesized from a bioactive natural product deoxyelephantopin (DET). Among them, DETD-35 showed potent antiproliferative activities against a panel of breast cancer cell lines including TNBC cell line MDA-MB-231, without inhibiting normal mammary cells M10. (Source: Molecular Oncology)
Source: Molecular Oncology - March 23, 2016 Category: Cancer & Oncology Authors: Kyoko Nakagawa-Goto, Jo-Yu Chen, Yu-Ting Cheng, Wai-Leng Lee, Munehisa Takeya, Yohei Saito, Kuo-Hsiung Lee, Lie-Fen Shyur Source Type: research
IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma
Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Dysregulation of SOCS protein expression in cancers can be one of the mechanisms that maintain STAT activation, but this mechanism is still poorly understood in oral squamous cell carcinoma (OSCC). Here, we report that SOCS2 protein is significantly downregulated in OSCC patients and its levels are inversely correlated with miR-424-5p expression. (Source: Molecular Oncology)
Source: Molecular Oncology - March 21, 2016 Category: Cancer & Oncology Authors: Hsuan-Yu Peng, Shih-Sheng Jiang, Jenn-Ren Hsiao, Michael Hsiao, Yuan-Ming Hsu, Guan-Hsun Wu, Wei-Min Chang, Jang-Yang Chang, Shiow-Lian Catherine Jin, Shine-Gwo Shiah Source Type: research
DNA damage signalling barrier, oxidative stress and treatment-relevant DNA repair factor alterations during progression of human prostate cancer
The DNA damage checkpoints provide an anti-cancer barrier in diverse tumour types, however this concept has remained unexplored in prostate cancer (CaP). Furthermore, targeting DNA repair defects by PARP1 inhibitors (PARPi) as a cancer treatment strategy is emerging yet requires suitable predictive biomarkers. To address these issues, we performed immunohistochemical analysis of multiple markers of DNA damage signalling, oxidative stress, DNA repair and cell cycle control pathways during progression of human prostate disease from benign hyperplasia, through intraepithelial neoplasia to CaP, complemented by genetic analyses...
Source: Molecular Oncology - March 3, 2016 Category: Cancer & Oncology Authors: Daniela Kurfurstova, Jirina Bartkova, Radek Vrtel, Alena Mickova, Alena Burdova, Dusana Majera, Martin Mistrik, Milan Kral, Frederic R. Santer, Jan Bouchal, Jiri Bartek Source Type: research
Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis
The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype litter mates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor in...
Source: Molecular Oncology - March 1, 2016 Category: Cancer & Oncology Authors: Daniel R. Carter, Selina K. Sutton, Marina Pajic, Jayne Murray, Eric O. Sekyere, Jamie Fletcher, Anneleen Beckers, Katleen De Preter, Frank Speleman, Rani E. George, Michelle Haber, Murray D. Norris, Belamy B. Cheung, Glenn M. Marshall Source Type: research
