Abstract
Cancer is the second leading cause of death worldwide. The survival of cancer patients depends on the efficacy of therapies and the development of resistance. There are many mechanisms involved in the acquisition of drug resistance by cancer cells, including the acquisition of stem-like features. Cancer stem cells (CSCs) represent a major source of tumor progression and treatment resistance. CSCs are a subpopulation of cancer cells having the abilities to self-renew and form spheres in vitro. Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cytosolic enzyme involved in the detoxification of cells from toxic aldehydes and belongs to the ALDH family. High ALDH1A1 activity is closely related to stemness phenotype of several tumors, possibly contributing to cancer progression and diffusion in the body. We have documented the contribution of ALDH1A1 in tumor angiogenesis in breast cancer cells by the activation of hypoxia inducible factor-1α and vascular endothelial growth factor signaling. This review discusses the involvement of ALDH1A1 in the development of different hallmarks of cancer to propose it as a novel putative target for cancer treatment to achieve better outcome. Here, we analyze the involvement of ALDH1A1 in the acquisition of stemness phenotype in tumor cells, the regulation of tumor angiogenesis and metastases, and the acquisition of anticancer drug resistance and immune evasion.
Highlights
Cancer is highly dynamic as tumor cells become more heterogeneous during the progression of the disease
We describe the contribution of Aldehyde dehydrogenase 1A1 (ALDH1A1) in tumor stemness and cancer progression, analyzing its involvement in angiogenesis, tumor spread, drug-resistance, and immuneevasion
The idea to develop therapeutic anti-cancer strategies that consider the heterogeneity of cancer is a medical option in the field of tumor biology and treatment
Summary
Cancer is highly dynamic as tumor cells become more heterogeneous during the progression of the disease. CSCs can be implicated in many hallmarks of cancer and recently CSC-directed therapies have been clinically developed[4] The involvement of these cells in chemoresistance is known, in particular by the maintenance in G0 phase; high expression of drug efflux pump, anti-apoptotic proteins, and scavenger molecules; more efficient DNA repair; and a protective microenvironment created by interaction with the tumor niche[5,6]. Aldehyde dehydrogenase 1A1 (ALDH1A1) is a protein that has been used to mark CSCs in several cancers, including leukemias and carcinomas of the breast, colon, liver, lung and pancreas, among others This enzyme belongs to the ALDH superfamily, composed of nicotinamide adenine dinucleotide (phosphate) (NAD(P)+)-dependent enzymes that catalyze the oxidation of exogenous and endogenous aldehydes to the respective carboxylic acids. We describe the contribution of ALDH1A1 in tumor stemness and cancer progression, analyzing its involvement in angiogenesis, tumor spread, drug-resistance, and immuneevasion
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
