Otofaji ve Kanser

Abstract

Programlanmış tip II hücre ölüm tipi olan otofaji kendi kendini yeme işlemidir. Açlık ve diğer stres durumlarında biyomoleküllerin yapı taşlarının bazal seviyelerini koruyan hücre içi bir geri dönüşüm sürecidir. Lizozom aracılı katabolik bir süreç olan otofaji hücresel homeostazın sürdürülmesinde önemli bir role sahiptir. Otofaji tiplerinden biri olan makrootofaji yolağı, iç ve dış sinyallerin uyarımı sonucunda hücre içi sindirilecek materyal (yanlış katlanmış ya da bozulmuş proteinler, hasarlı organeller, vb.) otofagozom içine alınarak, otofagozomun lizozomla birleşmesi sonucu lizozomal aktivite ile sindirilmesi sürecini içerir. Otofaji sinyal yolağı otofaji ile ilişkili genler (ATG’ler)’in ürünleri ile ilave proteinler ve otofaji ile ilişkili kinazlar tarafından düzenlenmektedir. Otofaji mekanizmasındaki bozukluklar kanserin de dahil olduğu çeşitli hastalıklarla ilişkilendirilmektedir. Tümör oluşumu sırasında otofajinin kanserin erken evresinde tümör baskılayıcı, ileri evrede ise tümörü teşvik edici ikili bir role sahip olduğu çeşitli çalışmalarla ortaya konmuştur. Otofajinin karmaşık yapısı ve kanserdeki bu ikili rolü sebebiyle mekanizmanın tam olarak aydınlatılması ve farklı kanserlerde hangi aşamada nasıl bir role sahip olduğunun belirlenmesi ya otofaji baskılayıcı ya da otofajiyi teşvik edici etkin tedavilerin geliştirilmesine olanak tanıyacaktır. Bu derlemede, makrootofaji sinyal yolağının moleküler mekanizması, otofajinin kanserdeki ikili rolü ve otofaji ile ilişkili kansere karşı geliştirilen tedavi yaklaşımları hakkında bilgiler verilmesi amaçlanmıştır.

Keywords

• otofaji
• makrootofaji
• kanser

Autophagy and Cancer

Abstract

Autophagy, type II programmed cell death, is a self-eating process. It is an intracellular recycling process that maintains basal levels of the building blocks of biomolecules during starvation and other stress situations. Autophagy, a lysosome-mediated catabolic process, has an important role in maintaining cellular homeostasis. The macroautophagy pathway, which is one of the autophagy types, includes the process of ingestion of the intracellular digestible material (misfolded or disrupted proteins, damaged organelles, etc.) into the autophagosome, followed by the fusion of the autophagosome with the lysosome, and the process of digestion with lysosomal activity by the stimulation of internal and external signals. The autophagy signaling pathway is regulated by products of autophagy-related genes (ATGs), additional proteins, and autophagy-related kinases. Disturbances in the autophagy mechanism are associated with various diseases, including cancer. Various studies have demonstrated that autophagy has a dual role as tumor suppressor in the early stage of cancer and tumor promoting in the advanced stage during tumor formation. Due to the complex structure of autophagy and its dual role in cancer, the full elucidation of the mechanism and the determination of what role it plays in different cancers will allow the development of effective treatments that either suppress autophagy or promote autophagy. In this review, it is aimed to give information about the molecular mechanism of the macroautophagy signaling pathway, the dual role of autophagy in cancer and the treatment approaches developed against autophagy-related cancer.

Keywords

• autophagy
• macroautophagy
• cancer

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