INTRODUCTION Autophagy is a self‐degrading adaptation mechanism in which cytoplasmic macromolecules and organelles are delivered to the lysosome for degradation and recycling. In a physiologic context autophagy could be both a cytoprotective driver and a programmed death facilitator. Sustained autophagy has been frequently detected in neoplastic transformation, even though its promoting role in cancer growth is not fully elucidated. In recent years, a significant correlation has emerged between molecular dysfunction leading to Tau protein accumulation and interference with mitosis progression. In our study we investigated the potential association between autophagy and Tau accumulation and its role during cell mitosis. METHODS We evaluated in vitro the role of autophagy in modulating the expression of Tau protein in prostate cancer cell lines, analyzing morphological and molecular consequences during mitosis. RESULTS Tau protein was expressed at low level in prostate cancer lines and western blot analysis showed in these cells the presence of several phosphorylated and oligomeric forms. The pharmacologic inhibition of autophagy by treatment with chloroquine, induced in cancer cells a reduction in proliferation with an increment of number of cells in G2/M phase of cell cycle. In addition, in these cells we observed an accumulation of Tau protein, with an increased expression of both phosphorylated and oligomeric forms. Immunofluorescence analysis of untreated cells revealed that Tau was expressed mainly in dividing cells where it was localized on mitotic spindle. Inhibition of autophagy determined an evident upregulation of Tau signal in dividing cells with a diffuse protein localization in cytoplasm. The accumulation of Tau protein was associated with the presence of aberrant mitotic spindles, with monoastral spindle as major unusual figure. CONCLUSIONS Our data indicate that autophagy could exert a promoting role in cancer growth facilitating degradation of Tau protein and thus blocking the inhibitory effect of accumulated Tau forms on mitosis. Thus, the understanding of molecular mechanisms underlying the homeostatic control of Tau protein degradation during cell mitosis could represent an important goal also in oncology research.
Inhibition of autophagy in prostate cancer cells stimulates Tau accumulation and aberrant mitotic spindle / MARTELLUCCI, STEFANO; Clementi, Letizia; Colapietro, Alessandro; Sabetta, Samantha; MATTEI, Vincenzo; Angelucci., Adriano. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 34:S1(2020).
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|Titolo:||Inhibition of autophagy in prostate cancer cells stimulates Tau accumulation and aberrant mitotic spindle|
MARTELLUCCI, STEFANO (Primo)
MATTEI, Vincenzo (Penultimo)
|Data di pubblicazione:||2020|
|Citazione:||Inhibition of autophagy in prostate cancer cells stimulates Tau accumulation and aberrant mitotic spindle / MARTELLUCCI, STEFANO; Clementi, Letizia; Colapietro, Alessandro; Sabetta, Samantha; MATTEI, Vincenzo; Angelucci., Adriano. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 34:S1(2020).|
|Appartiene alla tipologia:||01h Abstract in rivista|