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]
| Item Type: |
Tesi di dottorato
|
| Resource language: |
English |
| Title: |
Extra-ribosomal functions of ribosomal protein uL3 in response to drug-induced nucleolar stress in colon cancer cells lacking p53 |
| Creators: |
| Creators | Email |
|---|
| Pecoraro, Annalisa | annalisa.pecoraro@unina.it |
|
| Date: |
14 April 2021 |
| Number of Pages: |
99 |
| Institution: |
Università degli Studi di Napoli Federico II |
| Department: |
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 | UNSPECIFIED |
|
| Date: |
14 April 2021 |
| Number of Pages: |
99 |
| Keywords: |
ribosomal protein uL3; nucleolar stress; colon cancer |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/10 - Biochimica |
[error in script]
[error in script]
| Date Deposited: |
19 Apr 2021 07:54 |
| Last Modified: |
07 Jun 2023 11:03 |
| URI: |
http://www.fedoa.unina.it/id/eprint/13872 |
Collection description
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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