Abstract
Autophagy is a cellular “self-digestion” process known to be essential for various physiological and pathological pathways, including cancer, where its role appears to be context-dependent. In this work, we aimed to investigate the level of autophagy by evaluating the expression of key autophagy-related proteins (ATGs) in testicular germ cell tumors (TGCT) for which autophagy has been rarely investigated. We decided to use an immunohistochemical (IHC) staining approach employing a tissue microarray (TMA). Software-based evaluation of the integrated optical densities (IODs) of these proteins indicated a significant downregulation of ATG1, ATG5, and ATG16L1. Accordingly, reduced levels of microtubule-associated proteins 1A/1B light chain 3B (LC3B) were found to parallel increases in sequestosome-1 (SQSTM1 or p62), a protein normally degraded via autophagy, suggesting an in vivo reduction in autophagy with TGCT. Thus, our work provides evidence for a tumor suppressive function of autophagy in the development of TGCT and supports the concept of a context-dependent role of autophagy in tumorigenesis which is tumor type-dependent.
Highlights
Autophagy as a cellular catabolic process is essential at a basal level to ensure normal cellular homeostasis by the controlled degradation of cellular contents [1, 2]
Whether any Autophagy-related proteins (ATG) mRNA level differed between cancer and normal tissues could not be concluded owing to a lack of normal testis tissue samples
With tissue microarray (TMA) containing punches of 10 non-neoplastic testicular tissues retrieved from contralateral testicular biopsies of patients with testicular germ cell tumors (TGCT) and punches from 191 TGCT tumor patients, we employed immunohistochemical methods to stain for key autophagy regulators, ATG1, ATG5, and ATG16L1
Summary
Autophagy as a cellular catabolic process is essential at a basal level to ensure normal cellular homeostasis by the controlled degradation of cellular contents [1, 2]. It is highly regulated by the so-called ATGs as well as by class III PI3K and mTOR pathways [3]. Inhibition of autophagy has been proposed as a combination with conventional anticancer therapies for improving efficacy of the anti-cancer treatment and/or to overcome drug resistance [3, 4]. It is important to note the potential for dual roles of autophagy in cancer, both as “friend” and “foe” [3,4,5]
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