Expression of the cancer stem cell markers ABCG2 and OCT-4 in right-sided colon cancer predicts recurrence and poor outcomes

Hu, Jun; Li, Jian; Yue, Xin; Wang, Jiacang; Liu, Jianzhong; Sun, Lin; Kong, Dalu

doi:10.18632/oncotarget.15307

Cited by 53 publications

(32 citation statements)

References 42 publications

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“…The discovery of cancer stem cells and their therapy resistance as well as their self-renewal capacity has driven the attention towards this peculiar cell population. This specific subset of tumor cells has been shown to be prognostic for patients[ 28 , 29 ]. So far, CRC stem cells have been reported to be enriched for specific surface markers such as CD133, EphB2 high , EpCAM high , CD44 + , CD166 + , ALDH + , LGR5 + and CD44v6 +[30] .…”

Section: Introductionmentioning

confidence: 99%

Drug resistance and new therapies in colorectal cancer

Jeught

et al. 2018

WJG

461

220

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Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.

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Section: Introductionmentioning

confidence: 99%

Drug resistance and new therapies in colorectal cancer

Jeught

et al. 2018

WJG

461

220

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“…On the other hand, using an online transcriptome-level validation tool for predictive biomarkers [52], we found that ABCG2, associated with resistance to chemo-and radiotherapy [53] and RUNX2, which has been shown to chemosensitize breast cancer cells to neoadjuvant therapy [43], are more highly expressed in non-responder patients. Although not all the parameters analysed reached statistical significance, the observed trends could be corroborated using other probes available in the tool (data not shown).…”

Section: Discussionmentioning

confidence: 95%

Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer

et al. 2020

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Purpose Triple negative breast cancers (TNBCs) are enriched in cells bearing stem-like features, i.e., cancer stem cells (CSCs), which underlie cancer progression. Thus, targeting stemness may be an interesting treatment approach. The epigenetic machinery is crucial for maintaining the stemness phenotype. Bromodomain and extra-terminal domain (BET) epigenetic reader family members are emerging as novel targets for cancer therapy, and have already shown preclinical effects in breast cancer. Here, we aimed to evaluate the effect of the BET inhibitor JQ1 on stemness in TNBC. Methods Transcriptomic, functional annotation and qRT-PCR studies were performed on JQ1-exposed TNBC cells in culture. The results obtained were confirmed in spheroids and spheroid-derived tumours. In addition, limiting dilution, secondary and tertiary tumour sphere formation, matrigel invasion, immunofluorescence and flow cytometry assays were performed to evaluate the effect of JQ1 on CSC features. For clinical outcome analyses, the online tool Kaplan-Meier Plotter and an integrated response database were used. Results We found that JQ1 modified the expression of stemness-related genes in two TNBC-derived cell lines, MDA-MB-231 and BT549. Among these changes, the CD44 Antigen/CD24 Antigen (CD44/CD24) ratio and Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) expression level, i.e., both classical stemness markers, were found to be decreased by JQ1. Using a validated spheroid model to mimic the intrinsic characteristics of CSCs, we found that JQ1 decreased surface CD44 expression, inhibited self-renewal and invasion, and induced cell cycle arrest in G0/G1, thereby altering the stemness phenotype. We also found associations between four of the identified stemness genes, Gap Junction Protein Alpha 1 (GJA1), CD24, Epithelial Adhesion Molecule (EPCAM) and SRY-related HMG-box gene 9 (SOX9), and a worse TNBC patient outcome. The expression of another two of the stemness-related genes was found to be decreased by JQ1, i.e., ATP Binding Cassette Subfamily G Member 2 (ABCG2) and RUNX2, and predicted a low response to chemotherapy in TNBC patients, which supports a role for RUNX2 as a potential predictive marker for chemotherapy response in TNBC. Conclusions We identified a stemness-related gene panel associated with JQ1 and describe how this inhibitor modifies the stemness landscape in TNBC. Therefore, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell Leticia Serrano-Oviedo and Miriam Nuncia-Cantarero contributed equally to this work.

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“…That can be conceder as an environmental selective pressure, will eliminate cells which not capable of responding to it, leaving those with ABCG2 expression. The presence of this protein contributes to cell resistant to unfavorable stress render tumors capable or recurrent [33,34]. The aldehyde dehydrogenase (ALDH) is super-family of isoenzymes have an important function in protecting normal stem cells [35].…”

Section: Discussionmentioning

confidence: 99%

Starvation contributes to elevated levels of heat shock proteins and cancer stem cell markers in an esophageal cancer cell line.

Tawfeeq¹,

Mahmood²,

Abd-Alghni³

2018

biomedicalresearch

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The presence of cancer stem cells as a subpopulation residing in the apex of solid tumor cell hierarchy has been introduced as a new hypothesis capable of describing the ability of tumors to be more aggressive, highly metastasized, and chemo-radiotherapy resistant. The origin of these cells is still controversial: one hypothesis describes the stress conditions in the tumor microenvironment as one of the driving forces behind the existence of these cells. In this study, we test if nutrition depletion conditions (deprivation of serum and glucose) would be one of such forces. Esophagus adenocarcinoma cell line SKGT-4 was exposed to starvation by depleting glucose and fetal bovine serum from growth media at different times. The viability of the cells during this condition was determined by standard MTT assay and the cells' morphological changes were observed by crystal violet staining and trypan blue staining. The expression levels of stress-related proteins, heat shock protein 90 (HSP90) and heat shock protein 70 (HSP70), as well as some known cancer stem cell markers, CD44, ALDH1A1, and ABCG2, were determined using quantitative real-time PCR. Levels of necrosis and apoptosis were followed in cell populations under stress using a mixture of fluorescence staining and observation under a fluorescence microscope. The results indicated a loss of cell viability during the extended times of incubation in starved condition compared with the non-starved condition. Cells under starvation suffered from noticeable morphological changes combined with widespread necrosis and apoptosis. Levels of HSP90, HSP70, and cancer stem cell marker expression were significantly increased in starved condition compared with non-starved condition (p ≤ 0.01). In conclusion, although starvation as a result of serum and glucose depletion leads to induced necrosis and/or apoptosis in most of the cells, it may induce stress-resistant mechanisms in cells that remain viable (stress-resistant cells).

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Expression of the cancer stem cell markers ABCG2 and OCT-4 in right-sided colon cancer predicts recurrence and poor outcomes

Cited by 53 publications

References 42 publications

Drug resistance and new therapies in colorectal cancer

Drug resistance and new therapies in colorectal cancer

Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer

Starvation contributes to elevated levels of heat shock proteins and cancer stem cell markers in an esophageal cancer cell line.

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