Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin

Oxaliplatin is commonly known as a successful chemotherapy for advanced colorectal cancer, improving patient survival and eradicating micro-metastases, but its use in early stages remains controversial. Mitochondria fuel energy-intensive programs such as cell migration, yet how oxaliplatin regulates...

Descripción completa

Detalles Bibliográficos
Autores: Martinez-Bernabe, Toni, Morla-Barcelo, Pere Miquel, Fiore, Alessandra, Donadelli, Massimo, Roca, Pilar, Oliver, Jordi, Sastre-Serra, Jorge, Pons, Daniel G
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/26228
Acceso en línea:https://hdl.handle.net/20.500.13003/26228
Access Level:acceso abierto
Palabra clave:Cell Migration Assays
Colorectal Neoplasms
Oxaliplatin
Ensayos de Migración Celular
Neoplasias Colorrectales
Oxaliplatino
Cell migration
Colorectal cancer
Metabolic shift
p53-R273H
id ES_8e2f5bb679148152f4501b5b03cbb049
oai_identifier_str oai:docusalut.com:20.500.13003/26228
network_acronym_str ES
network_name_str España
repository_id_str
spelling Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatinMartinez-Bernabe, ToniMorla-Barcelo, Pere MiquelFiore, AlessandraDonadelli, MassimoRoca, PilarOliver, JordiSastre-Serra, JorgePons, Daniel GCell Migration AssaysColorectal NeoplasmsOxaliplatinEnsayos de Migración CelularNeoplasias ColorrectalesOxaliplatinoCell migrationColorectal cancerMetabolic shiftOxaliplatinp53-R273HOxaliplatin is commonly known as a successful chemotherapy for advanced colorectal cancer, improving patient survival and eradicating micro-metastases, but its use in early stages remains controversial. Mitochondria fuel energy-intensive programs such as cell migration, yet how oxaliplatin regulates the mitochondrial network in CRC - and how TP53 context shapes this - remains unclear. We investigated a matched pair of CRC cell lines from the same patient - SW480 (primary) and SW620 (lymph-node metastasis) - both harboring TP53-R273H mutation, to define differential responses in mitochondrial biogenesis, dynamics and respiration and the mechanisms underlying them. The results indicate that primary-derived colorectal cancer cell line increased cell migration, mitochondrial biogenesis, and mitochondrial respiration capacity in response to oxaliplatin through a new and firstly described gain-of-function (GOF) of p53-R273H. Additionally, in the primary-derived CRC line, oxaliplatin elicited fate heterogeneity - coexisting apoptotic and senescent fractions alongside an R273H-driven, bioenergetically primed migratory subpopulation - together with increased mitochondrial biogenesis and respiratory capacity; by contrast, the metastatic-derived line was more sensitive and displayed structural mitochondrial injury with reduced maximal respiration. More broadly, this work underscores the importance of p53 gain-of-function mutations in CRC: the same GOF (TP53-R273H) amplifies cell migration by coupling an enhanced mitochondrial biogenesis/OXPHOS program to motility. Oxaliplatin further accentuates this energetically primed, pre-metastatic state, arguing for mitochondrial-targeted combination strategies in early-stage CRC.20252025-10-2720252025-10-27research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/26228reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/262282026-06-22T12:44:07Z
dc.title.none.fl_str_mv Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
title Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
spellingShingle Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
Martinez-Bernabe, Toni
Cell Migration Assays
Colorectal Neoplasms
Oxaliplatin
Ensayos de Migración Celular
Neoplasias Colorrectales
Oxaliplatino
Cell migration
Colorectal cancer
Metabolic shift
Oxaliplatin
p53-R273H
title_short Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
title_full Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
title_fullStr Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
title_full_unstemmed Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
title_sort Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
dc.creator.none.fl_str_mv Martinez-Bernabe, Toni
Morla-Barcelo, Pere Miquel
Fiore, Alessandra
Donadelli, Massimo
Roca, Pilar
Oliver, Jordi
Sastre-Serra, Jorge
Pons, Daniel G
author Martinez-Bernabe, Toni
author_facet Martinez-Bernabe, Toni
Morla-Barcelo, Pere Miquel
Fiore, Alessandra
Donadelli, Massimo
Roca, Pilar
Oliver, Jordi
Sastre-Serra, Jorge
Pons, Daniel G
author_role author
author2 Morla-Barcelo, Pere Miquel
Fiore, Alessandra
Donadelli, Massimo
Roca, Pilar
Oliver, Jordi
Sastre-Serra, Jorge
Pons, Daniel G
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Cell Migration Assays
Colorectal Neoplasms
Oxaliplatin
Ensayos de Migración Celular
Neoplasias Colorrectales
Oxaliplatino
Cell migration
Colorectal cancer
Metabolic shift
Oxaliplatin
p53-R273H
topic Cell Migration Assays
Colorectal Neoplasms
Oxaliplatin
Ensayos de Migración Celular
Neoplasias Colorrectales
Oxaliplatino
Cell migration
Colorectal cancer
Metabolic shift
Oxaliplatin
p53-R273H
description Oxaliplatin is commonly known as a successful chemotherapy for advanced colorectal cancer, improving patient survival and eradicating micro-metastases, but its use in early stages remains controversial. Mitochondria fuel energy-intensive programs such as cell migration, yet how oxaliplatin regulates the mitochondrial network in CRC - and how TP53 context shapes this - remains unclear. We investigated a matched pair of CRC cell lines from the same patient - SW480 (primary) and SW620 (lymph-node metastasis) - both harboring TP53-R273H mutation, to define differential responses in mitochondrial biogenesis, dynamics and respiration and the mechanisms underlying them. The results indicate that primary-derived colorectal cancer cell line increased cell migration, mitochondrial biogenesis, and mitochondrial respiration capacity in response to oxaliplatin through a new and firstly described gain-of-function (GOF) of p53-R273H. Additionally, in the primary-derived CRC line, oxaliplatin elicited fate heterogeneity - coexisting apoptotic and senescent fractions alongside an R273H-driven, bioenergetically primed migratory subpopulation - together with increased mitochondrial biogenesis and respiratory capacity; by contrast, the metastatic-derived line was more sensitive and displayed structural mitochondrial injury with reduced maximal respiration. More broadly, this work underscores the importance of p53 gain-of-function mutations in CRC: the same GOF (TP53-R273H) amplifies cell migration by coupling an enhanced mitochondrial biogenesis/OXPHOS program to motility. Oxaliplatin further accentuates this energetically primed, pre-metastatic state, arguing for mitochondrial-targeted combination strategies in early-stage CRC.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-10-27
2025
2025-10-27
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/26228
url https://hdl.handle.net/20.500.13003/26228
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869413108235108352
score 15.81155

Similares en LA Referencia