Medicine and Health Sciences Commons^™

The Nogo Receptor Ngr2, A Novel Αvβ3 Integrin Effector, Induces Neuroendocrine Differentiation In Prostate Cancer, Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter Mccue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, …

Ctpathway: A Crosstalk-Based Pathway Enrichment Analysis Method For Cancer Research, Haizhou Liu, Mengqin Yuan, Ramkrishna Mitra, Xu Zhou, Min Long, Wanyue Lei, Shunheng Zhou, Yu-E Huang, Fei Hou, Christine M. Eischen, Wei Jiang

Department of Cancer Biology Faculty Papers

Background: Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated.

Methods: To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in …