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Medicine and Health Sciences

Thomas Jefferson University

Department of Cancer Biology Faculty Papers

2016

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A Neuronal Network Of Mitochondrial Dynamics Regulates Metastasis., M. Cecilia Caino, Jae Ho Seo, Angeline Aguinaldo, Eric Wait, Kelly G. Bryant, Andrew V. Kossenkov, James E. Hayden, Valentina Vaira, Annamaria Morotti, Stefano Ferrero, Silvano Bosari, Dmitry I. Gabrilovich, Lucia R. Languino, Andrew R. Cohen, Dario C. Altieri Dec 2016

A Neuronal Network Of Mitochondrial Dynamics Regulates Metastasis., M. Cecilia Caino, Jae Ho Seo, Angeline Aguinaldo, Eric Wait, Kelly G. Bryant, Andrew V. Kossenkov, James E. Hayden, Valentina Vaira, Annamaria Morotti, Stefano Ferrero, Silvano Bosari, Dmitry I. Gabrilovich, Lucia R. Languino, Andrew R. Cohen, Dario C. Altieri

Department of Cancer Biology Faculty Papers

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater …


Expression Of Μ-Protocadherin Is Negatively Regulated By The Activation Of The Β-Catenin Signaling Pathway In Normal And Cancer Colorectal Enterocytes., Lucia Montorsi, Sandra Parenti, Lorena Losi, Fabrizio Ferrarini, Claudia Gemelli, A Rossi, Gianrocco Manco, Stefano Ferrari, Bruno Calabretta, Enrico Tagliafico, Tommaso Zanocco-Marani, Alexis Grande Jun 2016

Expression Of Μ-Protocadherin Is Negatively Regulated By The Activation Of The Β-Catenin Signaling Pathway In Normal And Cancer Colorectal Enterocytes., Lucia Montorsi, Sandra Parenti, Lorena Losi, Fabrizio Ferrarini, Claudia Gemelli, A Rossi, Gianrocco Manco, Stefano Ferrari, Bruno Calabretta, Enrico Tagliafico, Tommaso Zanocco-Marani, Alexis Grande

Department of Cancer Biology Faculty Papers

Mu-protocadherin (MUCDHL) is an adhesion molecule predominantly expressed by colorectal epithelial cells which is markedly downregulated upon malignant transformation. Notably, treatment of colorectal cancer (CRC) cells with mesalazine lead to increased expression of MUCDHL, and is associated with sequestration of β-catenin on the plasma membrane and inhibition of its transcriptional activity. To better characterize the causal relationship between β-catenin and MUCDHL expression, we performed various experiments in which CRC cell lines and normal colonic organoids were subjected to culture conditions inhibiting (FH535 treatment, transcription factor 7-like 2 siRNA inactivation, Wnt withdrawal) or stimulating (LiCl treatment) β-catenin activity. We show here …