AMBRA1 and SQSTM1 expression pattern in prostate cancer.

Laura Falasca,Francesco Torino,Steno Sentinelli,Mario Patrizio,Vincenzo Pompeo,Laura De Salvo,Walter Malorni,Matteo Marconi,Cristiano Padula,Mauro Piacentini,Michele Gallucci,Manuela Costantini

doi:10.1007/s10495-015-1176-3

Abstract

Prostate cancer is among the most commonly diagnosed male diseases and a leading cause of cancer mortality in men. There is emerging evidence that autophagy plays an important role in malignant cell survival and offers protection from the anti-cancer drugs in prostate cancer cells. AMBRA1 and the autophagic protein sequestosome-1 (SQSTM1; p62) expression were evaluated by immunohistochemistry and western blot on tissue samples from both benign and malignant prostatic lesions. The data reported in this pilot study demonstrated an increased expression of AMBRA1 and SQSTM1, which were also associated with an accumulation of LC3II in prostate cancer but not in benign lesion. In the present study we found that: (i) at variance with benign lesion, prostate cancer cells underwent SQSTM1 accumulation, i.e., clearly displayed a defective autophagic process but, also, (ii) prostate cancer accumulated AMBRA1 and (iii) this increase positively correlated with the Gleason score. These results underscore a possible implication of autophagy in prostate cancer phenotype and of AMBRA1 as possible cancer progression biomarker in this malignancy.

Highlights

Autophagy is a cellular stress response and a quality control mechanism involved in the lysosomal degradation of cytosolic components in both physiological and pathological conditions [1]
In the present study we found that: (i) at variance with benign lesion, prostate cancer cells underwent SQSTM1 accumulation, i.e., clearly displayed a defective autophagic process but, (ii) prostate cancer accumulated AMBRA1 and (iii) this increase positively correlated with the Gleason score
The immune reactivity of AMBRA1 and SQSTM1 was localized in the cytoplasm of epithelial cells of Prostate cancer (PCa) and benign prostate hyperplasia (BPH) tissues, while no signals were detected in the normal prostatic tissues (Fig. 1a, b)

Summary

Introduction

Autophagy is a cellular stress response and a quality control mechanism involved in the lysosomal degradation of cytosolic components in both physiological and pathological conditions [1]. Aberrations in oncogenes and/or tumor suppressor genes frequently inhibit or impair the Apoptosis (2015) 20:1577–1586 autophagic process In this condition, the defective autophagic flux can lead to the accumulation of the cargobinding protein SQSTM1, which has been reported to represent a direct link between autophagy impairment and tumorigenesis [9, 10]. The defective autophagic flux can lead to the accumulation of the cargobinding protein SQSTM1, which has been reported to represent a direct link between autophagy impairment and tumorigenesis [9, 10] On these bases, some anticancer agents, e.g., the mammalian target of rapamycin (mTOR) inhibitors such as rapamycin and derivatives such as everolimus, have been introduced in the field of cancer treatments. These agents have been shown to modulate the activity of proteins involved in autophagic process, leading to the concept that its modulation might represent a valuable therapeutic target in patients affected by several malignancies, including prostate cancer [11, 12]

Objectives

Methods

Results

Conclusion