Oxidative Distress Induces Wnt/β-Catenin Pathway Modulation in Colorectal Cancer Cells: Perspectives on APC Retained Functions

Cancers

Teresa Catalano¹  Maria Carmela Di Marcantonio²  Rossano Lattanzio²  Federico Selvaggi³  Carmelo Moscatello³  Roberto Cotellese³  Gitana Maria Aceto³  Emira D’Amico³  Maria Cristina Curia³  Giuseppina Bologna⁴  Alessio Ferrone⁴  Paola Lanuti⁴ 

[1] Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy;Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;Department of Medicine and Aging Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;

关键词: colorectal cancer;    oxidative stress;    Wnt/β-Catenin;    APC;    gene expression;    protein expression;   

DOI  :  10.3390/cancers13236045

来源: DOAJ

【 摘 要 】

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 H₂O₂-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 H₂O₂ promote β-Catenin expression and modulate cytoplasmic APC protein. Furthermore, H₂O₂ 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.

【 授权许可】

Unknown