Clinical relevance of SOX proteins in gastric cancer

• Grant number: 17/02204-3
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: December 11, 2017
• End date: December 22, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcelo Lima Ribeiro
• Grantee: Marcelo Lima Ribeiro
• Visiting researcher: Ander Matheu Fernandez
• Visiting researcher institution: Instituto de Investigación Sanitaria Biodonostia (IIS Biodonostia), Spain
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Gastric cancer remains one of the leading causes of global cancer mortality. It has been shown that gastric cancer may originate from adult gastric stem cells and that it contains a subpopulation of cancer cells with stem cell characteristics, which are linked to Helicobacter pylori infection, therapy resistance and metastasis. Thus, the identification of transcription factors and related signal transduction pathways that regulate stem cell maintenance and lineage allocation is attractive from a clinical standpoint in that it may provide targets for novel cell- or drug-based therapies. SOX [sex-determining region Y (Sry) box-containing] genes are a family of transcription factors that are potent regulators of stem cell maintenance and cell fate decisions during homeostasis and play relevant roles in cancer initiation and progression in multiple organ systems, including the gastrointestinal tract. Professors Ribeiro and Matheu, as a consequence of the Ciencia sem fronteiras 300975/2014-7 project entitled "Análise Funcional das Proteínas SOX no Câncer Gástrico", have been actively collaborating in the last 3 years in order to (i) determine the function of SOX members in gastric cancer, (ii) define its relationship with Helicobacter pylori infection, the most common cause of gastric cancer (iii) understand the molecular mechanisms underlying SOX activities and how these mechanisms relate to cancer progression. They have obtained significant results, which have been published in 3 manuscripts in Cancer Research, American Journal of Cancer Research and Molecular Carcinogenesis journals and a book chapter revealing the impact of SOX9, SOX2 in gastric carcinogenesis, in addition to showing their interaction with DNA repair. Importantly, the Professors still have additional unpublished data, which they are planning to submit in 2017. Moreover, their collaboration extends the scientific area and during the last 3 years Dr. Matheu (i) gave classes in Universidade São Francisco graduation and Universidade Estadual de Campinas undergraduate and postgraduate courses (ii) received in his lab members from Dr. Ribeiro’s group, (iii) helped to supervise Dr. Ribeiro´s students (iv) offered input and advise in additional Dr. Ribeiro’s projects and (v) participated as collaborator and advisor in Dr. Ribeiro´s senior postdoctoral first national projects, helping them in their scientific career development. They plan to maintain and reinforce their collaboration during 2017 and this proposal is a major endevour in this direction since the award of the grant will enable to (i) support meetings to discuss research results, (ii) facilitate contacts to write the manuscripts of the pending results, (iii) create the scientific environment to develop novel ideas and projects, (iv) facilitate the classes that Dr. Matheu will give in Universidade São Francisco. (AU)