Ve to normal proteins, IDPs demonstrate increased plasticity and tend to participate in the dysregulation of many cellular processes that define cancer biology, including cellular proliferation and dedifferentiation. Building on this concept, Malaney and colleagues studied the protein suppressor and IDP, PTEN 74. They used PONDR-FIT software to develop a series of interactomes comprising the IDP network that included PTEN and associated interactors, including PTEN phosphorylating kinases. Other levels in the analysis accounted for mutated amino acid combinations favoring abnormal protein function by introducing hydrophobicity, aromaticity, and redox-sensitive properties properties. Forty PTEN-associated Ornipressin biological activity proteins emerged from the analysis, of which 25 appear to interact with the intrinsically disordered region of PTEN at the carboxy-tail. The interactome was also in agreement with a number of previous publications in the cancer literature: 13 cancer-related proteins were also identified as strong IDP candidates and, in turn, formed a small, but potentially important, “PTEN-Cancer interactome.” One evolving area of converging research streams is that of factors influencing treatment resistance to some cancers. As one example of this property of many malignancies, genetic data were collected from 71 patients registered in the Long-HER study, which characterized clinical responsiveness to the monoclonal antibody, trastuzumab, for the treatment of metastistic breast cancer. From this dataset, a number of expression profile differences involving PTEN and PTEN-associated genes were observed between treatment responders and non-responders, including intermediates involved in activation of the proliferative and anti-apoptotic kinase mammalian target of rapamycin (mTOR) 75. A number of reports have aimed to use similar methodologies to identify generic markers that distinguish tumor benignity from malignancy. For example, elevated concordance rates were observed in one study between tissue and plasma proteins Litronesib web differentially expressed in benign vs. malignant serous ovarian tumors and measured by liquid chromatography-mass spectrometry. Subsequent hierarchical pathway analysis focusing on 20 proteins suggested that 14-3-Author Manuscript Author Manuscript Author Manuscript Author ManuscriptWiley Interdiscip Rev Syst Biol Med. Author manuscript; available in PMC 2016 July 01.Wang et al.Pagezeta/delta, 14-3-3 beta/alpha, alpha-actinin 4, HSP60, and PCBP1 are candidate markers of tumor malignancy 76. Unopposed angiogenesis is yet another fundamental pathological mechanism responsible for growth and propagation of various solid tumors that has also been the subject of network analyses. Indeed, characterizing the protein-protein response pattern to vascular endothelial growth factor (VEGF) treatment in vascular endothelial cells in vitro has contributed to early iterations of the “angiome” 77. Others have developed networks focusing on identifying interactors of alternative, but critical, proangiogenic proteins 78, including MMPs 79, epidermal growth factor 80, vonWillebrand factor 81, and hypoxia-inducible factor (HIF)-1 82 to expand the number of potential treatment targets for various cancer subtypes, including prostate, pancreatic, and breast adenocarcinoma. Diseases of the gastrointestinal tract Ulcerative colitis and Crohn’s disease are two overlapping clinical pathophenotypes characterized by inflammatory changes to the colon in the former, and t.Ve to normal proteins, IDPs demonstrate increased plasticity and tend to participate in the dysregulation of many cellular processes that define cancer biology, including cellular proliferation and dedifferentiation. Building on this concept, Malaney and colleagues studied the protein suppressor and IDP, PTEN 74. They used PONDR-FIT software to develop a series of interactomes comprising the IDP network that included PTEN and associated interactors, including PTEN phosphorylating kinases. Other levels in the analysis accounted for mutated amino acid combinations favoring abnormal protein function by introducing hydrophobicity, aromaticity, and redox-sensitive properties properties. Forty PTEN-associated proteins emerged from the analysis, of which 25 appear to interact with the intrinsically disordered region of PTEN at the carboxy-tail. The interactome was also in agreement with a number of previous publications in the cancer literature: 13 cancer-related proteins were also identified as strong IDP candidates and, in turn, formed a small, but potentially important, “PTEN-Cancer interactome.” One evolving area of converging research streams is that of factors influencing treatment resistance to some cancers. As one example of this property of many malignancies, genetic data were collected from 71 patients registered in the Long-HER study, which characterized clinical responsiveness to the monoclonal antibody, trastuzumab, for the treatment of metastistic breast cancer. From this dataset, a number of expression profile differences involving PTEN and PTEN-associated genes were observed between treatment responders and non-responders, including intermediates involved in activation of the proliferative and anti-apoptotic kinase mammalian target of rapamycin (mTOR) 75. A number of reports have aimed to use similar methodologies to identify generic markers that distinguish tumor benignity from malignancy. For example, elevated concordance rates were observed in one study between tissue and plasma proteins differentially expressed in benign vs. malignant serous ovarian tumors and measured by liquid chromatography-mass spectrometry. Subsequent hierarchical pathway analysis focusing on 20 proteins suggested that 14-3-Author Manuscript Author Manuscript Author Manuscript Author ManuscriptWiley Interdiscip Rev Syst Biol Med. Author manuscript; available in PMC 2016 July 01.Wang et al.Pagezeta/delta, 14-3-3 beta/alpha, alpha-actinin 4, HSP60, and PCBP1 are candidate markers of tumor malignancy 76. Unopposed angiogenesis is yet another fundamental pathological mechanism responsible for growth and propagation of various solid tumors that has also been the subject of network analyses. Indeed, characterizing the protein-protein response pattern to vascular endothelial growth factor (VEGF) treatment in vascular endothelial cells in vitro has contributed to early iterations of the “angiome” 77. Others have developed networks focusing on identifying interactors of alternative, but critical, proangiogenic proteins 78, including MMPs 79, epidermal growth factor 80, vonWillebrand factor 81, and hypoxia-inducible factor (HIF)-1 82 to expand the number of potential treatment targets for various cancer subtypes, including prostate, pancreatic, and breast adenocarcinoma. Diseases of the gastrointestinal tract Ulcerative colitis and Crohn’s disease are two overlapping clinical pathophenotypes characterized by inflammatory changes to the colon in the former, and t.
