ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin

Publication date: May 2020Source: Biomedicine &Pharmacotherapy, Volume 125Author(s): Wei Wang, Shujin He, Renya Zhang, Jie Peng, Daolu Guo, Jinguo Zhang, Bo Xiang, Lei LiAbstractAldehyde dehydrogenase 1A1 (ALDH1A1) is a marker of cancer stem-like cells (CSCs), but knowledge about the molecular mechanism of ALDH1A1 in maintaining the properties of CSCs remains limited. ALDH1A1 immunohistochemistry was performed in esophageal squamous cell carcinoma (ESCC) tissues, Western blotting was used to detect relationship between ALDH1A1 and AKT or β-catenin. Subcutaneous transplantation of tumors and drug resistance, spherogenesis experiments were used to test the ESCC cell stemness. Co-IP and confocal were used to detected the co-localization of LADH1A1 and β-catenin. ALDH1A1 expression maintained the CSC properties of ESCC cells. It enhanced the chemo-resistance ability, clonogenicity, and spherogenesis in vitro and tumorigenicity in vivo. High ALDH1A1 expression is an adverse prognostic factor of ESCC patients. Small-molecule inhibitor NCT-501 down-regulates ALDH1A1 expression and inhibits the AKT-β-catenin signaling pathway. ALDH1A1 overexpression activates the AKT signaling pathway. ALDH1A1 interacts with β-catenin, co-localization in KYS-510 cells.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research

Related Links:

ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin. Biomed Pharmacother. 2020 Feb 07;125:109940 Authors: Wang W, He S, Zhang R, Peng J, Guo D, Zhang J, Xiang B, Li L Abstract Aldehyde dehydrogenase 1A1 (ALDH1A1) is a marker of cancer stem-like cells (CSCs), but knowledge about the molecular mechanism of ALDH1A1 in maintaining the properties of CSCs remains limited. ALDH1A1 immunohistochemistry was performed in esophageal squamous cell carcinoma (ESCC) tissues, Western blotting was used t...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
ConclusionsHSCT patients have an extremely high risk of developing pneumonia after esophagectomy, and the condition can easily become serious. Therefore, broad-spectrum antibiotics should be administered prophylactically to prevent severe pneumonia during the perioperative period in these patients.
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, abnormal fucosylation might participate in the progress of esophageal squamous cell carcinoma and tissue-specific transplantation antigen P35B may serve as a novel biomarker for prognosis of patients with esophageal squamous cell carcinoma. PMID: 29950151 [PubMed - in process]
Source: Technology in Cancer Research and Treatment - Category: Cancer & Oncology Authors: Tags: Technol Cancer Res Treat Source Type: research
ConclusionIn the present study, we demonstrate the establishment of a mouse model esophageal squamous cell carcinoma allowing transplantation into syngeneic mice with distant metastatic potential. We believe that the present syngeneic mouse model will have utility in various preclinical research fields, including cancer immunotherapy.
Source: Esophagus - Category: Gastroenterology Source Type: research
Desmoplasia, or deposition of connective tissue proper in the stroma, is a key feature of esophageal squamous cell carcinoma (ESCC), a common malignancy worldwide. The cellular component of connective tissue proper is comprised of fibroblasts, and cancer-associated fibroblasts (CAFs) are widely recognized as a major constituent of the tumor microenvironment (TME). The purpose of this study was to investigate the cross-talk between CAFs and tumor cells in ESCC, as well as identify factors that mediate this cross-talk and evaluate these factors as therapeutic targets in ESCC and potentially other squamous cell carcinomas.We ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Cell-Cell Signaling in the Tumor Microenvironment Source Type: research
This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis. Materials and Methods A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2?derived prostaglandin E2 (PGE2) were measured by quantitative re...
Source: Cancer Research and Treatment - Category: Cancer & Oncology Tags: Original Article Source Type: research
In conclusion, we have shown that expression of CD38 plays an important role in MDSC biology by promoting an enhanced immunosuppressive capacity and a more immature phenotype in vivo. We have also detected an expansion of CD38-positive MDSCs in peripheral blood of advanced stage cancer patients and propose targeting CD38 in vivo as an approach to cancer therapy.Supported by NCI P01CA098101.Citation Format: Tatiana A. Karakasheva, Todd J. Waldron, Evgeniy Eruslanov, Ju-Seog Lee, Shaun O'Brien, Devraj Basu, Sunil Singhal, Fabio Malavasi, Anil K. Rustgi. CD38-expressing myeloid-derived suppressor cells promote tumor growth in...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Immunology Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Drugs & Pharmacology | Esophagus Cancer | Skin Cancer | Squamous Cell Carcinoma | Transplants