更新于：2024-11-01

ALDH3A1

更新于：2024-11-01

基本信息

别名

Aldehyde dehydrogenase 3、aldehyde dehydrogenase 3 family member A1、Aldehyde dehydrogenase family 3 member A1

+ [4]

简介

ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde (Probable). They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation (Probable). Oxidizes medium and long chain aldehydes into non-toxic fatty acids (PubMed:1737758). Preferentially oxidizes aromatic aldehyde substrates (PubMed:1737758). Comprises about 50 percent of corneal epithelial soluble proteins (By similarity). May play a role in preventing corneal damage caused by ultraviolet light (By similarity).

关联

项与 ALDH3A1 相关的药物

CB29

靶点

ALDH3A1

作用机制

ALDH3A1抑制剂

在研机构

The Indiana University School of Medicine

原研机构

The Indiana University School of Medicine

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ALDH3A1 相关的临床结果

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100 项与 ALDH3A1 相关的转化医学

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0 项与 ALDH3A1 相关的专利（医药）

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525

项与 ALDH3A1 相关的文献（医药）

2024-11-01·Life Sciences

ALDH and cancer stem cells: Pathways, challenges, and future directions in targeted therapy

Review

作者: Kokkanti, Rekha Rani ; Wang, Qi-En ; Nuguri, Shreya Madhav ; Pandey, Prashant ; Lavudi, Kousalya

Human ALDH comprise 19 subfamilies in which ALDH1A1, ALDH1A3, ALDH3A1, ALDH5A1, ALDH7A1, and ALDH18A1 are implicated in CSC. Studies have shown that ALDH can also be involved in drug resistance and standard chemotherapy regimens are ineffective in treating patients at the stage of disease recurrence. Existing chemotherapeutic drugs eliminate the bulk of tumors but are usually not effective against CSC which express ALDH+ population. Henceforth, targeting ALDH is convincing to treat the patient's post-relapse. Combination therapies that interlink signaling mechanisms seem promising to increase the overall disease-free survival rate. Therefore, targeting ALDH through ALDH inhibitors along with immunotherapies may create a novel platform for translational research. This review aims to fill in the gap between ALDH1 family members in relation to its cell signaling mechanisms, highlighting their potential as molecular targets to sensitize recurrent tumors and bring forward the future development concerning the current progress and draw backs. This review summarizes the role of cancer stem cells and their upregulation by maintaining the tumor microenvironment in which ALDH is specifically highlighted. It discusses the regulation of ALDH family proteins and the crosstalk between ALDH and CSC in relation to cancer metabolism. Furthermore, it establishes the correlation between ALDH involved signaling mechanisms and their specific targeted inhibitors, as well as their functional modularity, bioavailability, and mechanistic role in various cancers.

2024-10-25·Investigative Ophthalmology & Visual Science

PAX6–WNK2 Axis Governs Corneal Epithelial Homeostasis

Article

作者: Liu, Jiafeng ; Chen, Xiangjun ; Zhu, Liqiong ; Li, Lingyu ; Liu, Dongmei ; Mo, Kunlun ; Huang, Ying ; Du, Xinyue ; Wu, Siqi ; Ouyang, Hong ; Ji, Jianping ; Lan, Xihong ; Zhan, Yu ; Guo, Huizhen ; Chen, Chaoqun ; Yuan, Jin ; Tan, Jieying ; Wang, Li

PurposeLimbal stem/progenitor cells (LSCs) continuously proliferate and differentiate to replenish the corneal epithelium and play a vital role in corneal function and normal vision. A previous study revealed that paired box 6 (PAX6) is a master transcription factor involved in determining the fate of corneal epithelial cells (CECs). However, the molecular events downstream of PAX6 remain largely unknown. In this study, we aimed to clarify the regulation network of PAX6 in driving CEC differentiation.MethodsAn air-liquid culture system was used to differentiate LSCs into mature CECs. Specific targeting PAX6 short-hairpin RNAs were used to knock down PAX6 in LSC. RNA sequencing (RNA-seq) was used to analyze shPAX6-transfected CECs and CEC differentiation-associated genes to identify the potential downstream targets of PAX6. RNA-seq analysis, quantitative real-time PCR, and immunofluorescence staining were performed to clarify the function of WNK lysine deficient protein kinase 2 (WNK2), a downstream target of PAX6, and its relationship with corneal diseases.ResultsWNK2 expression increased during CEC differentiation and decreased upon PAX6 depletion. The distribution of WNK2 was specifically limited to the central corneal epithelium and suprabasal layer of the limbus. Knockdown of WNK2 impaired the expression of CEC-specific markers (KRT12, ALDH3A1, and CLU), disrupted the corneal differentiation process, and activated the terms of keratinization, inflammation, and cell proliferation, consistent with PAX6-depleted CEC and published microbial keratitis. Thus, aberrant expression of WNK2 was linked to corneal ulcers.ConclusionsAs a downstream target of PAX6, WNK2 plays an essential role in corneal epithelial cell differentiation and maintenance of corneal homeostasis.

2024-10-21·Oncogene

ALDH1A3 is the switch that determines the balance of ALDH+ and CD24−CD44+ cancer stem cells, EMT-MET, and glucose metabolism in breast cancer

Article

作者: Cahill, Hannah F ; Wasson, Marie-Claire D ; Dean, Cheryl A. ; Dean, Cheryl A ; Coyle, Krysta M ; MacLean, Maya R ; Dahn, Margaret L ; Morales-Quintanilla, Fiorella ; Power Coombs, Melanie R. ; Walker, Olivia L ; Wasson, Marie-Claire D. ; Arun, Raj Pranap ; Walker, Olivia L. ; Cruickshank, Brianne M. ; Marcato, Paola ; Power Coombs, Melanie R ; Cruickshank, Brianne M ; Dahn, Margaret L. ; MacLean, Maya R. ; Fernando, Wasundara ; Coyle, Krysta M. ; Cahill, Hannah F.

AbstractPlasticity is an inherent feature of cancer stem cells (CSCs) and regulates the balance of key processes required at different stages of breast cancer progression, including epithelial-to-mesenchymal transition (EMT) versus mesenchymal-to-epithelial transition (MET), and glycolysis versus oxidative phosphorylation. Understanding the key factors that regulate the switch between these processes could lead to novel therapeutic strategies that limit tumor progression. We found that aldehyde dehydrogenase 1A3 (ALDH1A3) regulates these cancer-promoting processes and the abundance of the two distinct breast CSC populations defined by high ALDH activity and CD24−CD44+ cell surface expression. While ALDH1A3 increases ALDH+ breast cancer cells, it inversely suppresses the CD24−CD44+ population by retinoic acid signaling-mediated gene expression changes. This switch in CSC populations induced by ALDH1A3 was paired with decreased migration but increased invasion and an intermediate EMT phenotype. We also demonstrate that ALDH1A3 increases oxidative phosphorylation and decreases glycolysis and reactive oxygen species (ROS). The effects of ALDH1A3 reduction were countered with the glycolysis inhibitor 2-deoxy-D-glucose (2DG). In cell culture and tumor xenograft models, 2DG suppresses the increase in the CD24−CD44+ population and ROS induced by ALDH1A3 knockdown. Combined inhibition of ALDH1A3 and glycolysis best reduces breast tumor growth and tumor-initiating cells, suggesting that the combination of targeting ALDH1A3 and glycolysis has therapeutic potential for limiting CSCs and tumor progression. Together, these findings identify ALDH1A3 as a key regulator of processes required for breast cancer progression and depletion of ALDH1A3 makes breast cancer cells more susceptible to glycolysis inhibition.