SUMOylation regulates the aggressiveness of breast cancer-associated fibroblasts DOI Creative Commons
Angélica Martínez‐López,

Guiomar Infante,

Marina Mendiburu‐Eliçabe

et al.

Cellular Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cellular component in tumor microenvironment (TME). CAFs contribute to tumorigenesis and have been proposed as targets for anticancer therapies. Similarly, dysregulation of SUMO machinery components can disrupt balance SUMOylation, contributing drug resistance various cancers, including breast cancer. We explored role SUMOylation evaluated its potential a therapeutic strategy used pharmacological genetic approaches analyse functional crosstalk between cells CAFs. treated with SUMO1 inhibitor ginkgolic acid (GA) at two different concentrations conditioned media was proliferation, migration, invasion cancer from molecular subtypes. Additionally, we performed quantitative proteomics (SILAC) study differential signalling pathways expressed low or high GA. confirmed these results both vitro vivo. Moreover, samples metastatic patients evaluate use GA strategy. Inhibition induces death but does not affect viability CAFs, indicating that resistant this therapy. While CAF is unaffected, CAF-conditioned (CM) altered by GA, impacting cell behaviour ways depending on overall degree which SUMO1-SUMOylated proteins dysregulated. Breast lines exhibited concentration-dependent response At concentration (10 µM), there an increase migration cells. However, higher (30 processes were inhibited. analysis development revealed 10 µM tumors heavier greater metastasis compared µM). some effects could be explained alteration activity GTPase Rac1 activation AKT pathway. The obtained using SILAC suggest affected differentially, possibly influencing secretome Treatment demonstrated inhibition alternative highlights importance microenvironment, specifically cancer-associated (CAFs). Targeting affects their manner, regulating protumorigenic properties

Language: Английский

SENP3 induced HADHA deSUMOylation enhances intrahepatic cholangiocarcinoma chemotherapy sensitivity via fatty acid oxidation DOI

Jijun Shan,

Zhiwen Chen, Mo Chen

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217770 - 217770

Published: May 1, 2025

Language: Английский

Citations

0
An annotated biobank of triple negative breast cancer patient-derived xenografts featuring treatment-naive and longitudinal samples throughout neoadjuvant chemotherapy DOI Creative Commons
Amanda L. Rinkenbaugh, Yuan Qi, Shirong Cai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

SUMMARY Triple negative breast cancer (TNBC) that fails to respond neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies eradicate chemoresistant disease requires experimental models recapitulate the heterogeneity characteristic of TNBC. To end, we established a biobank 92 orthotopic patient-derived xenograft (PDX) TNBC from tumors 75 patients enrolled in ARTEMIS clinical trial ( NCT02276443 ) at MD Anderson Cancer Center, including 12 longitudinal sets generated serial patient biopsies collected throughout NACT and metastatic disease. Models were both chemosensitive tumors, nearly 30% PDX capable lung metastasis. Comprehensive molecular profiling demonstrated conservation genomes transcriptomes between corresponding with representation all major transcriptional subtypes. Transcriptional changes observed highlight dysregulation pathways associated DNA integrity, extracellular matrix interactions, ubiquitin-proteasome system, epigenetics, inflammatory signaling. These alterations reveal complex network adaptations chemoresistance. This provides valuable resource for tackling most pressing issues facing management TNBC, namely chemoresistance

Language: Английский

Citations

0
SUMOylation regulates the aggressiveness of breast cancer-associated fibroblasts DOI Creative Commons
Angélica Martínez‐López,

Guiomar Infante,

Marina Mendiburu‐Eliçabe

et al.

Cellular Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cellular component in tumor microenvironment (TME). CAFs contribute to tumorigenesis and have been proposed as targets for anticancer therapies. Similarly, dysregulation of SUMO machinery components can disrupt balance SUMOylation, contributing drug resistance various cancers, including breast cancer. We explored role SUMOylation evaluated its potential a therapeutic strategy used pharmacological genetic approaches analyse functional crosstalk between cells CAFs. treated with SUMO1 inhibitor ginkgolic acid (GA) at two different concentrations conditioned media was proliferation, migration, invasion cancer from molecular subtypes. Additionally, we performed quantitative proteomics (SILAC) study differential signalling pathways expressed low or high GA. confirmed these results both vitro vivo. Moreover, samples metastatic patients evaluate use GA strategy. Inhibition induces death but does not affect viability CAFs, indicating that resistant this therapy. While CAF is unaffected, CAF-conditioned (CM) altered by GA, impacting cell behaviour ways depending on overall degree which SUMO1-SUMOylated proteins dysregulated. Breast lines exhibited concentration-dependent response At concentration (10 µM), there an increase migration cells. However, higher (30 processes were inhibited. analysis development revealed 10 µM tumors heavier greater metastasis compared µM). some effects could be explained alteration activity GTPase Rac1 activation AKT pathway. The obtained using SILAC suggest affected differentially, possibly influencing secretome Treatment demonstrated inhibition alternative highlights importance microenvironment, specifically cancer-associated (CAFs). Targeting affects their manner, regulating protumorigenic properties

Language: Английский

Citations

0