Clinicopathological significance of cancer stem-like cell markers in high-grade neuroendocrine carcinoma of the lung

Morise, Masahiro; Hishida, Tomoyuki; Takahashi, Akiko; Ohe, Yuichiro; Nagai, Kanji; Ishii, Genichiro

doi:10.1007/s00432-015-1985-3

Cited by 13 publications

(10 citation statements)

References 43 publications

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“…The role of FOXD3 in stem cells is further demonstrated by facilitating the exit from naive pluripotency and transition to a primed pluripotent state . Recent studies have suggested parallels between embryonic stem cells and TICs, which is highlighted by the shared transcription factors involved . The deregulation of FOXD3 is implicated in the tumorigenesis of gastric cancer, melanoma, and breast cancer .…”

Section: Introductionmentioning

confidence: 99%

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

et al. 2019

Stem Cells

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The tumor-initiating cells (TICs) are a cell population that can initiate tumor occurrence, mediate drug resistance, and give rise to metastasis. FOXD3 is a forkhead box (Fox) transcription factor family that regulates the pluripotency of embryonic stem cell and tumorigenicity. However, it is unclear whether FOXD3 plays any role in TIC and tumor metastasis. The functional analysis of FOXD3 was performed by oncospheres formation and redifferentiation, drug resistance assay, and cell migration. Global genomic RNA-Seq and ChIP-Seq analysis were used to identify the direct target of FOXD3 in lung cancer. We demonstrated that downregulation of FOXD3 in TICs was positively correlated with higher histologic grades and positive lymph node metastasis. FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, we found that FOXD3 represses WDR5, which regulates TIC-related signaling pathway. Moreover, WDR5 were positively correlated with the TIC abundance and tumor progression. Besides, patients with high expression of WDR5 presented a poorer overall survival. FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer. STEM CELLS 2019;37:582-592 SIGNIFICANCE STATEMENTCurrently, it is unclear whether FOXD3 plays any role in the tumor-initiating cells (TIC) and tumor metastasis. This study found that FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, it was found that FOXD3 represses WDR5, which regulates the TIC-related signaling pathway. Collectively, the work defined that FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer.

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Section: Introductionmentioning

confidence: 99%

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

et al. 2019

Stem Cells

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“…It has been demonstrated that the CSC marker Nanog upregulates FAK, which, in turn, phosphorylates Nanog in CRC cell lines [59]. Upregulation and activation of FAK has also been observed in the presence of Oct 3/4-surexpressing glioblastoma primary cell cultures [245]. CD133, another CSC marker, enhanced cells migration through Src-FAK signaling activation [246].…”

Section: Regulation Of Cancer Stem Cellsmentioning

confidence: 99%

Role of Focal Adhesion Kinase in Small-Cell Lung Cancer and Its Potential as a Therapeutic Target

Nana

Vanderputten

Ocak

2019

Cancers

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Small-cell lung cancer (SCLC) represents 15% of all lung cancers and it is clinically the most aggressive type, being characterized by a tendency for early metastasis, with two-thirds of the patients diagnosed with an extensive stage (ES) disease and a five-year overall survival (OS) as low as 5%. There are still no effective targeted therapies in SCLC despite improved understanding of the molecular steps leading to SCLC development and progression these last years. After four decades, the only modest improvement in OS of patients suffering from ES-SCLC has recently been shown in a trial combining atezolizumab, an anti-PD-L1 immune checkpoint inhibitor, with carboplatin and etoposide, chemotherapy agents. This highlights the need to pursue research efforts in this field. Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that is overexpressed and activated in several cancers, including SCLC, and contributing to cancer progression and metastasis through its important role in cell proliferation, survival, adhesion, spreading, migration, and invasion. FAK also plays a role in tumor immune evasion, epithelial-mesenchymal transition, DNA damage repair, radioresistance, and regulation of cancer stem cells. FAK is of particular interest in SCLC, being known for its aggressiveness. The inhibition of FAK in SCLC cell lines demonstrated significative decrease in cell proliferation, invasion, and migration, and induced cell cycle arrest and apoptosis. In this review, we will focus on the role of FAK in cancer cells and their microenvironment, and its potential as a therapeutic target in SCLC.

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“…It was interesting to detect differences in CD44, ALDH1 protein and STAT3 gene expression between the UWG02CTC and UWG02ASC, which probably reflects the different pathways of tumour cell dissemination. Of note, higher expression of CSC markers and key stem pathways was also found on UWG02CTC versus UWG01CTC, despite ALDH1, CD44, and CD133 reported as CSC markers in both adenocarcinomas and high grade neuroendocrine tumours 33,34 .…”

Section: Discussionmentioning

confidence: 88%

Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer

Brungs

Minaei

Piper

et al. 2020

Sci Rep

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Circulating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug sensitivity testing, and investigation of the pathobiology of metastases. We report for the first time the establishment and characterisation of two continuous CTC lines from patients with gastroesophageal cancer. The two cell lines (designated UWG01CTC and UWG02CTC) demonstrated rapid tumorigenic growth in immunodeficient mice and exhibit distinct genotypic and phenotypic profiles which are consistent with the tumours of origin. UWG02CTC exhibits an epcAM+, cytokeratin+, CD44+ phenotype, while UWG01CTC, which was derived from a patient with metastatic neuroendocrine cancer, displays an EpCAM−, weak cytokeratin phenotype, with strong expression of neuroendocrine markers. Further, the two cell lines show distinct differences in drug and radiation sensitivity which match differential cancer-associated gene expression pathways. This is strong evidence implicating EpCAM negative CTCs in metastasis. These novel, well characterised, long-term ctc cell lines from gastroesophageal cancer will facilitate ongoing research into metastasis and the discovery of therapeutic targets.

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Clinicopathological significance of cancer stem-like cell markers in high-grade neuroendocrine carcinoma of the lung

Cited by 13 publications

References 43 publications

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5

Role of Focal Adhesion Kinase in Small-Cell Lung Cancer and Its Potential as a Therapeutic Target

Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer

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