Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance

Nairuz, Tahsin; Mahmud, Zimam; Manik, Rasel Khan; Kabir, Yearul

doi:10.1007/s12015-023-10529-x

Cited by 12 publications

(8 citation statements)

References 264 publications

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“…The concept of cancer stemness is based on the experimental evidence that only a small subset of cells within a tumour has capacity at any given time to generate new tumours and that the bulk of the tumour cell population has limited potency. The consequence of this so-called “cancer stem cell hypothesis” for cancer therapy is that it is only a small subset of malignant cells that are responsible for metastatic seeding and disease relapse following therapy and it is this sub-population (which exhibits drug resistance properties) that should be targeted to improve patient outcomes [ 131 , 132 ].…”

Section: Bcl3 and Cancermentioning

confidence: 99%

Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age

Seaton,

Smith,

Brancale

et al. 2024

Mol Cancer

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In the early 1990’s a group of unrelated genes were identified from the sites of recurring translocations in B-cell lymphomas. Despite sharing the nomenclature ‘Bcl’, and an association with blood-borne cancer, these genes have unrelated functions. Of these genes, BCL2 is best known as a key cancer target involved in the regulation of caspases and other cell viability mechanisms. BCL3 on the other hand was originally identified as a non-canonical regulator of NF-kB transcription factor pathways – a signaling mechanism associated with important cell outcomes including many of the hallmarks of cancer. Most of the early investigations into BCL3 function have since focused on its role in NF-kB mediated cell proliferation, inflammation/immunity and cancer. However, recent evidence is coming to light that this protein directly interacts with and modulates a number of other signaling pathways including DNA damage repair, WNT/β-catenin, AKT, TGFβ/SMAD3 and STAT3 – all of which have key roles in cancer development, metastatic progression and treatment of solid tumours. Here we review the direct evidence demonstrating BCL3’s central role in a transcriptional network of signaling pathways that modulate cancer biology and treatment response in a range of solid tumour types and propose common mechanisms of action of BCL3 which may be exploited in the future to target its oncogenic effects for patient benefit.

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Section: Bcl3 and Cancermentioning

confidence: 99%

Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age

Seaton,

Smith,

Brancale

et al. 2024

Mol Cancer

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“…Since metastasis and EMT, as well as recurrence and therapy resistance, are attributed to cancer stem cells (CSCs) (31,32), we studied the correlation of the 5 genes with regulators of CSCs. This analysis revealed that several stem cell markers were positively and significantly correlated with the 5 genes (Fig.…”

Section: Ankrd6 and Itih3 In Gc Progression Metastasis And Emtmentioning

confidence: 99%

Identification of a novel gene signature related to prognosis and metastasis in gastric cancer

Matheu,

Elizazu,

Otaegi-Ugartemendia

et al. 2023

Preprint

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Background: Gastric Cancer (GC) presents poor outcome, which is consequence of the high incidence of recurrence and metastasis at early stages. GC patients presenting recurrent or metastatic disease display a median life expectancy of only 8 months. The mechanisms underlying GC progression remain poorly understood. Methods: We took advantage of public available GC datasets from TCGA using GEPIA, and identified the matched genes among the 100 genes most significantly associated with overall survival (OS) and disease free survival (DFS). Results were confirmed in ACRG cohort and in over 2,000 GC cases obtained from several cohorts integrated using our own analysis pipeline. The Kaplan-Meier method and multivariate Cox regression analyses were used for prognostic significance and linear modelling and correlation analyses for association with clinic-pathological parameters and biological hallmarks. In vitro and in vivo functional studies were performed in GC cells with candidate genes and the related molecular pathways were studied by RNA sequencing. Results: High expression of ANKRD6, ITIH3, SORCS3, NPY1R and CCDC178 individually and as a signature was associated with poor prognosis and recurrent disease in GC. Among the 5 genes, ANKRD6, ITIH3 and NPY1R represented independent prognostic factors determined through multivariate Cox regression analyses. Moreover, the expression of ANKRD6 and ITIH3 was significantly higher in metastasis and its levels associated to EMT and stemness markers. Moreover, ANKRD6 silencing in GC metastatic cells showed impairment in GC tumorigenic activity and EMT in functional studies in vivo and in molecular pathways in transcriptomic studies. Conclusions: Our study identified a novel signature involved in GC malignancy and prognosis, and revealed a novel pro-metastatic role of ANKRD6 in GC.

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“…BBOX1-AS1 has been shown to upregulate PTCH1 by sponging miR-506-5p, which in turn upregulates EIF5A, stabilizing PTCH1 mRNA and ultimately activating the Hedgehog signaling pathway [ 42 ]. By modulating this critical signaling pathway, BBOX1-AS1 can impact ESCC cell proliferation and stemness, both crucial processes involved in cancer development [ 70 – 72 ].…”

Section: Bbox1-as1 Influences the Signaling Pathwaysmentioning

confidence: 99%

A review on the role of gamma-butyrobetaine hydroxylase 1 antisense RNA 1 in the carcinogenesis and tumor progression

Hu,

Liu,

Zhou

et al. 2023

Cancer Cell Int

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Gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1), located on human chromosome 11 p14, emerges as a critical player in tumorigenesis with diverse oncogenic effects. Aberrant expression of BBOX1-AS1 intricately regulates various cellular processes, including cell growth, epithelial–mesenchymal transition, migration, invasion, metastasis, cell death, and stemness. Notably, the expression of BBOX1-AS1 was significantly correlated with clinical-pathological characteristics and tumor prognoses, and it could also be used for the diagnosis of lung and esophageal cancers. Through its involvement in the ceRNA network, BBOX1-AS1 competitively binds to eight miRNAs in ten different cancer types. Additionally, BBOX1-AS1 can directly modulate downstream protein-coding genes or act as an mRNA stabilizer. The implications of BBOX1-AS1 extend to critical signaling pathways, including Hedgehog, Wnt/β-catenin, and MELK/FAK pathways. Moreover, it influences drug resistance in hepatocellular carcinoma. The present study provides a systematic review of the clinical significance of BBOX1-AS1’s aberrant expression in diverse tumor types. It sheds light on the intricate molecular mechanisms through which BBOX1-AS1 influences cancer initiation and progression and outlines potential avenues for future research in this field.

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Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance

Cited by 12 publications

References 264 publications

Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age

Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age

Identification of a novel gene signature related to prognosis and metastasis in gastric cancer

A review on the role of gamma-butyrobetaine hydroxylase 1 antisense RNA 1 in the carcinogenesis and tumor progression

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