Cancer Stem Cells in Intrahepatic Cholangiocarcinoma; Their Molecular Basis, and Therapeutic Implications

Tamai, Keiichi; Fujimori, Haruna; Mochizuki, Mai; Satoh, Kennichi

doi:10.3389/fphys.2021.824261

Cited by 2 publications

(1 citation statement)

References 57 publications

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“…Cancer tissue consists of heterogeneous cell types, and each subpopulation has plasticity to turn into the others. Cancer stem cells (CSCs) are a subpopulation that possesses therapeutic resistance and tumor reconstruction capability and are responsible for cancer progression [ 18 ‒ 20 ]. Considering that ELF4 was reported to affect cancer stemness in many cancers [ 21 , 22 ], we performed relevant in vitro and in vivo assays.…”

Section: Discussionmentioning

confidence: 99%

ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9

Xu,

Sun,

et al. 2023

ABBS

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Esophageal squamous cell carcinoma (ESCC) commonly has aggressive properties and a poor prognosis. Investigating the molecular mechanisms underlying the progression of ESCC is crucial for developing effective therapeutic strategies. Here, by performing transcriptome sequencing in ESCC and adjacent normal tissues, we find that E74-like transcription factor 4 (ELF4) is the main upregulated transcription factor in ESCC. The results of the immunohistochemistry show that ELF4 is overexpressed in ESCC tissues and is significantly correlated with cancer staging and prognosis. Furthermore, we demonstrate that ELF4 could promote cancer cell proliferation, migration, invasion, and stemness by in vivo assays. Through RNA-seq and ChIP assays, we find that the stemness-related gene fucosyltransferase 9 ( FUT9 ) is transcriptionally activated by ELF4. Meanwhile, ELF4 is verified to affect ESCC cancer stemness by regulating FUT9 expression. Overall, we first discover that the transcription factor ELF4 is overexpressed in ESCC and can promote ESCC progression by transcriptionally upregulating the stemness-related gene FUT9 .

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Section: Discussionmentioning

confidence: 99%

ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9

Xu,

Sun,

et al. 2023

ABBS

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A live single-cell reporter system reveals drug-induced plasticity of a cancer stem cell-like population in cholangiocarcinoma

Kongtanawanich,

Prasopporn,

Jamnongsong

et al. 2024

Sci Rep

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Cancer stem cells (CSC) play an important role in carcinogenesis and are acknowledged to be responsible for chemoresistance in cholangiocarcinoma (CCA). Studying CCA CSC has been challenging, due to lack of consensus CSC markers, and to their plastic nature. Since dual expression of the core pluripotent factors SOX2/OCT4 has been shown to correlate with poor outcome in CCA patients, we selected the SOX2/OCT4 activating short half-life GFP-based live reporter (SORE6-dsCopGFP) to study CSC dynamics at the single-cell level. Transduction of five human CCA cell lines resulted in the expression of 1.8–13.1% GFP-positive (SORE6 POS ) cells. By live imaging, we found that SORE6 POS CCA cells possess self-renewal capacity and that they can be induced to differentiate. Significantly, the SORE6 POS cells were highly tumorigenic, both in vitro and in vivo, thus implicating the characteristics of primary CSCs. When we then analyzed for selected CSC-related markers, we found that the majority of both CD133 + /CD44 + , and CD133 + /LGR5 + CCA cells were SORE6 POS cells. Exposing transduced cells to standard CCA chemotherapy revealed higher growth rate inhibition at 50% (GR 50 s) for SORE6 POS cells compared to GFP-negative (SORE6 NEG ) ones indicating that these CSC-like cells were more resistant to the treatment. Moreover, the chemotherapy induced SORE6 POS from SORE6 NEG cells, while retaining the existing SORE6 POS population. Finally, treatment of transduced cells with CDK4/6 inhibitors in vitro for 3 days resulted in a lowered CSC number in the culture. Thus, applying a live reporter system allowed us to elucidate the stem cell diversity and drug-induced plasticity of CCA CSCs. These findings have clear implications for future management of such patients. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-73581-8.

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Cancer Stem Cells in Intrahepatic Cholangiocarcinoma; Their Molecular Basis, and Therapeutic Implications

Cited by 2 publications

References 57 publications

ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9

ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9

A live single-cell reporter system reveals drug-induced plasticity of a cancer stem cell-like population in cholangiocarcinoma

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