Pecoraro, Annalisa (2021) Extra-ribosomal functions of ribosomal protein uL3 in response to drug-induced nucleolar stress in colon cancer cells lacking p53. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Extra-ribosomal functions of ribosomal protein uL3 in response to drug-induced nucleolar stress in colon cancer cells lacking p53 |
| Autori: | Autore Email Pecoraro, Annalisa annalisa.pecoraro@unina.it |
| Data: | 14 Aprile 2021 |
| Numero di pagine: | 99 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Farmacia |
| Dottorato: | Scienza del farmaco |
| Ciclo di dottorato: | 33 |
| Coordinatore del Corso di dottorato: | nome email D'Auria, Maria Valeria mariavaleria.dauria@unina.it |
| Tutor: | nome email Russo, Giulia [non definito] |
| Data: | 14 Aprile 2021 |
| Numero di pagine: | 99 |
| Parole chiave: | ribosomal protein uL3; nucleolar stress; colon cancer |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/10 - Biochimica |
| Depositato il: | 19 Apr 2021 07:54 |
| Ultima modifica: | 07 Giu 2023 11:03 |
| URI: | http://www.fedoa.unina.it/id/eprint/13872 |
Abstract
Beyond its canonical role in ribosome biogenesis, the nucleolus operates as a first-responder to stress stimuli that impair cell growth leading to a cellular condition, known as nucleolar stress, that is able to activate p53-dependent or p53-independent stress response signaling pathways. In this condition a subset of RPs translocates to the nucleoplasm where can exert their extra-ribosomal functions leading to cell cycle arrest and/or apoptosis. Among these RPs, we have indicated ribosomal protein uL3 (RPL3) as a key mediator of nucleolar stress pathway induced by chemotherapeutics as 5-Fluorouracile, Actinomycin D, and Oxaliplatin independently from p53 status. Here, we investigated more in depth the extra-ribosomal functions of uL3 in response to drug-induced nucleolar stress in colon cancer cells lacking p53 (HCT 116p53-/-). In addition, we have identified a strictly correlation between uL3 expression levels and drug sensitivity. Specifically, in our experimental model, the lower expression of uL3 is associated to enhancement of autophagic flux and epithelial-mesenchymal transition (EMT) phenotype resulting in Actinomycin D resistance. These observations imply a possibility that silencing of uL3 might increase the resistance of p53-deleted colon cancer cells to drug treatment through autophagy activation, enhancement in cell motility and EMT phenotype. In conclusion, our data might have a considerable value in the development of new targeted anticancer therapies for colorectal tumors lacking functional p53 and showing low expression levels of uL3 protein.
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