Aldehyde dehydrogenase 1: A specific cancer stem cell marker for human colorectal carcinoma

Zhou, Fei; Mu, Yindong; Liang, Jun; Liu, Zhi‐Xin; Zhou, Dan; Ning, Wenlong; Li, Yuezhen; Ding, Dong; Zhang, Jifei

doi:10.3892/mmr.2015.3195

Cited by 15 publications

(9 citation statements)

References 29 publications

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“…ALDH1A1 is a member of the ALDH1 family and a key marker of tumor stem cells, which is closely linked to the biological characteristics of tumor stem cells. As ALDH1 + cells have previously demonstrated a strong ability to self‐replicate and are tumorigenic, ALDH1 activity is considered to be a common marker of cancer stem cells (Douville et al, ; Zhou et al, ). The expression of ALDH1A1 in NPC tissue has been shown to be increased, which was related to the biological characteristics of tumor stem cells (You and Yang, ; Hou et al, ).…”

Section: Discussionmentioning

confidence: 99%

NOR1 Suppresses Cancer Stem‐Like Cells Properties of Tumor Cells via the Inhibition of the AKT‐GSK‐3β‐Wnt/β‐catenin‐ALDH1A1 Signal Circuit

Wei

Man

Chen

et al. 2017

Journal Cellular Physiology

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Cancer stem cells (CSCs) play a key role in tumor radiotherapy and chemotherapy resistance, relapse, and metastasis, and are primarily maintained in a resting state in vivo. The failure of conventional therapies to target CSCs is the main cause of treatment failure. The discovery of CSCs in nasopharyngeal carcinoma (NPC) tumors is becoming more prevalent; however, the understanding of the mechanisms underlying the maintenance of tumor stemness is still limited. We previously cloned NOR1, a tumor suppressor gene downregulated in NPC cell lines and tissues. In this study, we demonstrate that Wnt/β-catenin and ALDH1A1 form a signal circuit and that NOR1 antagonizes the tumor stem cell-like phenotype in NPC cell lines: the ectopic overexpression of NOR1 reduced β-catenin and ALDH1A1 expression; β-catenin/TCF4 targeted the regulation of ALDH1A1 transcription in NPC cells; silencing ALDH1A1 reduced AKT (total and phosphorylated) and GSK-3β (phosphorylated) expression; and eventually feedback decreased β-catenin expression levels. We also found that NOR1 expression decreased cancer stem-like cell properties of NPC cells, reduced their ability to form tumor spheroids in vitro, reduced tumorigenicity in nude mice in vivo, and increased sensitivity to chemotherapy agents. Taken together, our findings illustrated a new function of NOR1 that suppresses cancer stem-like cell properties in tumor cells by inhibiting the AKT-GSK-3β-Wnt/β-catenin-ALDH1A1 signal circuit. The study suggests that NOR1 deletion expression in NPC cells may be a potential molecular target for cancer stem cell therapy. J. Cell. Physiol. 232: 2829-2840, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

NOR1 Suppresses Cancer Stem‐Like Cells Properties of Tumor Cells via the Inhibition of the AKT‐GSK‐3β‐Wnt/β‐catenin‐ALDH1A1 Signal Circuit

Wei

Man

Chen

et al. 2017

Journal Cellular Physiology

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“…However, the role of retinal as an antiproliferative agent in OS has not been studied. Based on the fact that retinal can be transformed to retinoic acid by ALDH, and ALDH activity is typically higher in cancer stem cells [ 9 , 15 , 18 ], we investigated the effect that retinal would have on highly metastatic OS cells.…”

Section: Discussionmentioning

confidence: 99%

Retinal Targets ALDH Positive Cancer Stem Cell and Alters the Phenotype of Highly Metastatic Osteosarcoma Cells

Patel

Mektepbayeva³

et al. 2015

Sarcoma

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Aldehyde dehydrogenase (ALDH) is a cancer stem cell marker. Retinoic acid has antitumor properties, including the induction of apoptosis and inhibition of proliferation. Retinal, the precursor of retinoic acid, can be oxidized to retinoic acid by dehydrogenases, including ALDH. We hypothesized that retinal could potentially be transformed to retinoic acid with higher efficiency by cancer stem cells, due to the higher ALDH activity. We previously observed that ALDH activity is greater in highly metastatic K7M2 osteosarcoma (OS) cells than in nonmetastatic K12 OS cells. We also demonstrated that ALDH activity correlates with clinical metastases in bone sarcoma patients, suggesting that ALDH may be a therapeutic target specific to cells with high metastatic potential. Our current results demonstrated that retinal preferentially affected the phenotypes of ALDH-high K7M2 cells in contrast to ALDH-low K12 cells, which could be mediated by the more efficient transformation of retinal to retinoic acid by ALDH in K7M2 cells. Retinal treatment of highly metastatic K7M2 cells decreased their proliferation, invasion capacity, and resistance to oxidative stress. Retinal altered the expression of metastasis-related genes. These observations indicate that retinal may be used to specifically target metastatic cancer stem cells in OS.

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“…Several potential stem-like markers have been used to identify stem cells in adenomas/CRC. LGR5 and ALDH1 are the two most promising and established stem-like markers and have been frequently used [ 3 , 5 , 7 , 10 , 15 ]. Studies have reported that LGR5 and ALDH1 expression can reflect the changes in stem-like cells during the process of colorectal tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

“…This adenoma-carcinoma sequence provides an ideal opportunity to investigate the changes that occur during the development of CRC. Although many molecular, genetic and immunological alterations that are involved in this sequence have been identified [ 1 – 3 ], the exact mechanisms of the adenoma-carcinoma transition are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Temporal and spatial changes of cells positive for stem-like markers in different compartments and stages of human colorectal adenoma-carcinoma sequence

Cui

Zhu

et al. 2017

Oncotarget

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Considerable evidence supports the idea that stem-like cells may play an essential role during the development of colorectal cancer (CRC). To accomplish this aim, we use immunohistochemistry (IHC) and double IHC with different potential stem-like markers, anti-musashi (Msi), anti-CD133, anti- LGR5 and anti-ALDH1 to examine the presentation of stem-like cells in different compartments including adenoma/CRC epithelium, transitional crypts and tumor stroma in colorectal adenoma and CRC. The results showed that cells positive for stem-like markers were remarkably increased in number and frequently observed in the adenoma/CRC epithelium, transitional crypts and tumor stroma. Notably, the population of cells positive for stem-liker markers was expanded from the base to the middle part of the transitional crypt in both adenoma and CRC tissues, reflecting that stem-like cells are likely involved in the process of colorectal tumorigenesis. Counting results showed that the grading scores of cells positive for LGR5 and ALDH1 in the adenoma/CRC epithelium were significantly increased relative with the control epithelium, and associated with the degree of dysplasia in the adenoma and node involvement in the CRC (all P < 0.05). In addition, the density of cells positive for stem–like markers in the adenomatous/cancerous stroma was also increased and paralleled an increase in the density of proliferative stromal cells labeled by PCNA, which were primarily identified as vimentin positive fibroblasts. Our results have revealed a changed temporal and spatial presentation of stem-like markers in different stages of human colorectal adenoma-carcinoma sequence, which might be a hallmark of the adenoma-carcinoma transition.

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Aldehyde dehydrogenase 1: A specific cancer stem cell marker for human colorectal carcinoma

Cited by 15 publications

References 29 publications

NOR1 Suppresses Cancer Stem‐Like Cells Properties of Tumor Cells via the Inhibition of the AKT‐GSK‐3β‐Wnt/β‐catenin‐ALDH1A1 Signal Circuit

NOR1 Suppresses Cancer Stem‐Like Cells Properties of Tumor Cells via the Inhibition of the AKT‐GSK‐3β‐Wnt/β‐catenin‐ALDH1A1 Signal Circuit

Retinal Targets ALDH Positive Cancer Stem Cell and Alters the Phenotype of Highly Metastatic Osteosarcoma Cells

Temporal and spatial changes of cells positive for stem-like markers in different compartments and stages of human colorectal adenoma-carcinoma sequence

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