HEИндивидуална стипендия2023–2025

SIRT7-LC · Role of the SIRT7-NPM-c-Myc pathway in lung cancer

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-09-01 → 2025-08-31
Финансиране от ЕС: 165 313 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Ензимът SIRT7 и неговата роля в ядърцето на клетката се анализират, за да се разбере как влияе върху развитието на рака на белия дроб. Познаването на тези молекулярни механизми помага за създаването на по-ефективни и персонализирани стратегии за лечение.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Role of the SIRT7-NPM-c-Myc pathway in lung cancer

Lung cancer remains one of the most devastating diseases worldwide and is the leading cause of cancer-related death in both men and women. Within the European Union, it ranks as the third most common cancer among women and the second among men. Despite advances in diagnosis and treatment, the survival rate of lung cancer patients remains alarmingly low, with fewer than one in five individuals surviving more than five years after diagnosis. Understanding the molecular mechanisms that drive this disease is therefore crucial for developing more effective and personalized therapeutic strategies. In recent years, a family of enzymes known as sirtuins has attracted increasing attention for their ability to regulate essential cellular processes such as metabolism, stress response, and genome stability. Among them, Sirtuin 7 (SIRT7) has emerged as a complex and multifunctional enzyme capable of acting either as a promoter or a suppressor of tumor progression, depending on the cellular context. However, its precise role in lung cancer advancement remains poorly understood. SIRT7 is primarily located in the nucleolus, a compartment within the cell nucleus that—beyond its classical role in ribosome production—is now recognized as a key coordinator of processes linked to cancer initiation and development. By regulating proteins that control cell growth and stress responses, the nucleolus functions as a central hub in tumor biology. This evidence suggests that SIRT7 may influence lung cancer advancement, at least in part, by controlling these nucleolar functions. The SIRT7-LC project was established to investigate how SIRT7 contributes to lung cancer development and to identify the molecular mechanisms through which it exerts its effects. In particular, the project explored how SIRT7 modulates the activity of nucleophosmin (NPM), a multifunctional nucleolar protein that finely regulates the balance between tumor-suppressive and pro-oncogenic factors within the nucleolus, thereby affecting cancer cell growth and survival. Specifically, the overall objective of SIRT7-LC was to gain a deeper understanding of how SIRT7-mediated deregulation of nucleolar functions influences lung cancer progression, and to assess whether targeting SIRT7 could represent a viable strategy to limit disease advancement and improve patient outcomes.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Lung cancer is the second cause of death due to malignancy and diagnosed patients rarely survive beyond two years. Thus, unveiling the molecular mechanisms underlying lung tumorigenesis is imperative for development of novel therapeutic approaches. The nucleolar protein nucleophosmin (NPM) plays critical roles in cancer progression and is often deregulated in human malignancies. NPM employs distinct mechanisms to control cancer cells growth including regulation of the proto-oncogene c-Myc, a transcription factor often aberrantly activated in lung cancer. Recent studies highlighted the fundamental impact of post-translational modifications in controlling NPM functions. NPM is a deacetylation target of Sirtuin 7 (SIRT7), a member of a class of NAD+ dependent histone/protein deacetylases collectively known as sirtuins. Deacetylation of NPM by SIRT7 is fundamental to control NPM subcellular localization and stimulate NPM-mediated cellular stress responses. SIRT7 also acts as a potent oncogene in different malignancies although through still poorly characterized mechanisms. Thus, SIRT7-LC aims to characterize the impact of the SIRT7-NPM axis on regulation of c-Myc pro-oncogenic activities and its impact on lung cancer cells proliferation in vitro and in vivo, as well as possible aberrant activation of this pathway in human lung cancers and its correlation with prognosis. Thus, SIRT7-LC may lead to identification of novel molecular mechanisms sustaining lung cancer growth that could be targeted for therapeutic interventions. Dr. Alejandro Vaquero, a world-leading expert in the sirtuins field, will supervise this project. His competence in the field together with my expertise in characterization of mouse models of diseases will undoubtedly ensure successful realization of the proposed project, expanding my scientific knowledge, increasing my visibility as scientist and contributing to my development as a fully independent investigator.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS · BadalonaКоординаторИспания