Summary of project PR002250
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002250. The data can be accessed directly via it's Project DOI: 10.21228/M8SJ9Z This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002250 |
| Project DOI: | doi: 10.21228/M8SJ9Z |
| Project Title: | Multilevel Plasticity and Altered Glycosylation Drive Aggressiveness in Hypoxic and Glucose-Deprived Bladder Cancer Cells |
| Project Type: | Multilevel Plasticity and Altered Glycosylation Drive Aggressiveness in Hypoxic and Glucose-Deprived Bladder Cancer Cells |
| Project Summary: | Bladder tumours with aggressive characteristics often present microenvironmental niches marked by low oxygen levels (hypoxia) and limited glucose supply due to inadequate vascularization. The molecular mechanisms facilitating cellular adaptation to these stimuli remain largely elusive. Employing a multi-omics approach, we discovered that hypoxic and glucose-deprived cancer cells enter a quiescent state supported by mitophagy, fatty acid β-oxidation, and amino acid catabolism, concurrently enhancing their invasive capabilities. Reoxygenation and glucose restoration efficiently reversed cell quiescence without affecting cellular viability, highlighting significant molecular plasticity in adapting to microenvironmental challenges. Furthermore, cancer cells exhibited substantial perturbation of protein O-glycosylation, leading to simplified glycophenotypes with shorter glycosidic chains. Exploiting glycoengineered cell models, we established that immature glycosylation contributes to reduced cell proliferation and increased invasion. Our findings collectively indicate that hypoxia and glucose deprivation trigger cancer aggressiveness, reflecting an adaptive escape mechanism underpinned by altered metabolism and protein glycosylation, providing grounds for clinical intervention. |
| Institute: | Portuguese Oncology Institute of Porto (IPO-Porto) |
| Department: | IPO Porto Research Center |
| Laboratory: | Lab 2 |
| Last Name: | Peixoto |
| First Name: | Andreia |
| Address: | Rua Dr. António Bernardino de Almeida |
| Email: | andreia.peixoto@ipoporto.min-saude.pt |
| Phone: | 225084000 |
| Funding Source: | The authors acknowledge FCT/MCTES funding within the projects RESOLVE (PTDC/MED-OUT/2512/2021) and REVERENT (2022.03621.PTDC; DOI 10.54499/2022.03621.PTDC) and funding for the IPO research center (PEst-OE/SAU/UI0776/201, CI-IPOP-29-2016-2022, CI-IPOP-58-2016-2022), for CQUM (UID/QUI/00686/2020), and the LAQV research unit (UIDB/50006/2020 | UIDP/50006/2020). |
| Contributors: | Andreia Peixoto, Dylan Ferreira, Andreia Miranda, Marta Relvas-Santos, Rui Freitas, Tim S. Veth, Andreia Brandão, Eduardo Ferreira, Paula Paulo, Marta Cardoso, Cristiana Gaiteiro, Sofia Cotton, Janine Soares, Luís Lima, Filipe Teixeira, Rita Ferreira, Carlos Palmeira, Albert J. R. Heck, Maria José Oliveira, André M. N. Silva, Lúcio Lara Santos, José Alexandre Ferreira |
Summary of all studies in project PR002250
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003639 | Multilevel Plasticity and Altered Glycosylation Drive Aggressiveness in Hypoxic and Glucose-Deprived Bladder Cancer Cells | Homo sapiens | Portuguese Oncology Institute of Porto (IPO-Porto) | MS | 2025-01-20 | 1 | 12 | Uploaded data (2.4G)* |
