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Oxidative Distress Induces Wnt/β-Catenin Pathway Modulation in Colorectal Cancer Cells: Perspectives on APC Retained Functions
| Content Provider | MDPI |
|---|---|
| Author | D’Amico, Emira Catalano, Teresa Moscatello, Carmelo Marcantonio, Maria Carmela Di Ferrone, Alessio Bologna, Giuseppina Selvaggi, Federico Lanuti, Paola Cotellese, Roberto Curia, Maria Cristina Lattanzio, Rossano Aceto, Gitana Maria |
| Copyright Year | 2021 |
| Description | Colorectal cancer (CRC) is a multistep process that arises in the colic tissue microenvironment. Oxidative stress plays a role in mediating CRC cell survival and progression, as well as promoting resistance to therapies. CRC progression is associated with Wnt/β-Catenin signaling dysregulation and loss of proper APC functions. Cancer recurrence/relapse has been attributed to altered ROS levels, produced in a cancerous microenvironment. The effect of oxidative distress on Wnt/β-Catenin signaling in the light of APC functions is unclear. This study evaluated the effect of $H_{2}O_{2}$-induced short-term oxidative stress in HCT116, SW480 and SW620 cells with different phenotypes of APC and β-Catenin. The modulation and relationship of APC with characteristic molecules of Wnt/β-Catenin were assessed in gene and protein expression. Results indicated that CRC cells, even when deprived of growth factors, under acute oxidative distress conditions by $H_{2}O_{2}$ promote β-Catenin expression and modulate cytoplasmic APC protein. Furthermore, $H_{2}O_{2}$ induces differential gene expression depending on the cellular phenotype and leading to favor both Wnt/Catenin-dependent and -independent signaling. The exact mechanism by which oxidative distress can affect Wnt signaling functions will require further investigation to reveal new scenarios for the development of therapeutic approaches for CRC, in the light of the conserved functions of APC. |
| Starting Page | 6045 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers13236045 |
| Journal | Cancers |
| Issue Number | 23 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-11-30 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Colorectal Cancer Oxidative Stress Wnt/β-catenin Apc Gene Expression Protein Expression Microenvironment |
| Content Type | Text |
| Resource Type | Article |
