TCTN2: a novel tumor marker with oncogenic properties

// David Cano-Rodriguez 2, * , Susanna Campagnoli 1, * , Alberto Grandi 1 , Matteo Parri 1 , Elisa De Camilli 3 , Chaojun Song 4 , Boquan Jin 4 , Aurelien Lacombe 5 , Andrea Pierleoni 1, 9 , Mauro Bombaci 7 , Chiara Cordiglieri 7 , Marcel HJ Ruiters 2 , Giuseppe Viale 3, 6 , Luigi Terracciano 5 , Paolo Sarmientos 1 , Sergio Abrignani 7 , Guido Grandi 8 , Piero Pileri 1 , Marianne G. Rots 2 and Renata Grifantini 1, 7 1 Externautics SpA, Siena, Italy 2 Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands 3 Department of Pathology, European Institute of Oncology, Milan, Italy 4 Department of Immunology, The Fourth Military Medical University, Xi’an, China 5 Institute of Pathology, University Hospital Basel, Basel, Switzerland 6 Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy 7 Istituto Nazionale Genetica Molecolare, Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy 8 Centre for Integrative Biology - CIBIO, University of Trento, Trento, Italy 9 Present affiliation: European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK * These authors have contributed equally to this work Correspondence to: Renata Grifantini, email: grifantini@ingm.org Piero Pileri, email: piero.pileri@externautics.com Marianne G. Rots, email: m.g.rots@umcg.nl Keywords: TCTN2; cancer; biomarker; oncogene; epigenetic editing Received: February 17, 2017     Accepted: July 25, 2017     Published: August 24, 2017 ABSTRACT Tectonic family member 2 ( TCTN2 ) encodes a transmembrane protein that belongs to the tectonic family, which is involved in ciliary functions. Previous studies have demonstrated the role of tectonics in regulating a variety of signaling pathways at the transition zone of cilia. However, the role of tectonics in cancer is still unclear. Here we identify that TCTN2 is overexpressed in colorectal, lung and ovary cancers. We show that different cancer cell lines express the protein that localizes at the plasma membrane, facing the intracellular milieu. TCTN2 over-expression in cancer cells resulted in an increased ability to form colonies in an anchorage independent way. On the other hand, downregulation of TCTN2 using targeted epigenetic editing in cancer cells significantly reduced colony formation, cell invasiveness, increased apoptosis and impaired assembly of primary cilia. Taken together, our results indicate that TCTN2 acts as an oncogene, making it an interesting cancer-associated protein and a potential candidate for therapeutic applications.