Cellular, transcriptomic and isoform heterogeneity of breast cancer cell line revealed by full-length single-cell RNA sequencing

Wu, Shaocheng; Zhang, Hongjiu; Fouladdel, Shamileh; Li, Hongyang; Keller, Evan T.; Wicha, Max S.; Omenn, Gilbert S.; Azizi, Ebrahim

doi:10.1016/j.csbj.2020.03.005

Cited by 28 publications

(23 citation statements)

References 70 publications

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“…Various transcriptomic signature-based metrics have helped quantify the EMT status of cells along a continuous spectrum; these methods exhibit concordant results among themselves [ 104 ]. Characterization of hybrid E/M cells in tumor samples is gaining importance in terms of deciding the course of treatment and thus unravelling the contributions of cells with different EMT phenotypes in metastasis, drug resistance, and disease aggressiveness – an important aspect enabled only by such high-throughput single-cell analysis [ [105] , [106] , [107] ].…”

Section: Defining Partial Emtmentioning

confidence: 99%

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Saxena

Jolly

Balamurugan

2020

Translational Oncology

153

112

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Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.

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Section: Defining Partial Emtmentioning

confidence: 99%

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Saxena

Jolly

Balamurugan

2020

Translational Oncology

153

112

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“…The study of Sharma et al revealed the multi-level tumor evolution of lung squamous cell carcinoma based on cell subclones closely related to tumor-immune cell interactions [ 194 ]. In the study of Wu et al, the immunological interactions between breast cancer cells and TME were proved, showing the ability of scRNA-Seq for analyzing tumor in a dynamic state [ 195 ].…”

Section: Applications Of Transcriptome Analysis In Oncologymentioning

confidence: 99%

Current Achievements and Applications of Transcriptomics in Personalized Cancer Medicine

Supplitt

Karpiński

Sasiadek

et al. 2021

IJMS

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Over the last decades, transcriptome profiling emerged as one of the most powerful approaches in oncology, providing prognostic and predictive utility for cancer management. The development of novel technologies, such as revolutionary next-generation sequencing, enables the identification of cancer biomarkers, gene signatures, and their aberrant expression affecting oncogenesis, as well as the discovery of molecular targets for anticancer therapies. Transcriptomics contribute to a change in the holistic understanding of cancer, from histopathological and organic to molecular classifications, opening a more personalized perspective for tumor diagnostics and therapy. The further advancement on transcriptome profiling may allow standardization and cost reduction of its analysis, which will be the next step for transcriptomics to become a canon of contemporary cancer medicine.

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“…Furthermore, 3 distinct gene expression profiles were displayed by migratory cells associated with BCSCs, including enhanced antioxidant defense, low mitochondrial fragmentation, and downregulation of proteasome genes [189] . The BCSCs in TNBC were also heterogenous and associated with 3 distinct patterns of expression of stemness, including EMT, MET, and dual EMT-MET [190] . The EMT-CSC gene expression signature was associated with the expression ITGA6, EPCAM, CCND1, CD44, EGFR, CDH1, CCND1, and MKI67 [190] .…”

Section: Origin Of Breast Cancersmentioning

confidence: 99%

“…The BCSCs in TNBC were also heterogenous and associated with 3 distinct patterns of expression of stemness, including EMT, MET, and dual EMT-MET [190] . The EMT-CSC gene expression signature was associated with the expression ITGA6, EPCAM, CCND1, CD44, EGFR, CDH1, CCND1, and MKI67 [190] .…”

Section: Origin Of Breast Cancersmentioning

confidence: 99%

Breast cancers, mammary stem cells, and cancer stem cells, characteristics, and hypotheses

Taurin

Alkhalifa

2020

Neoplasia

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Highlights Breast cancer is a complex disease arising from the association and cumulation of multiple genetic alterations and environmental factors likely to alter cellular functions. The implication of stem cells in breast cancer’s origin and development has been debated for many years. Analogies between stem cells and cancer cells can be drawn on many levels. Importantly not all cancer cells are stem cells or exhibit properties similar to stem cells. There is no universal cell surface marker of the breast cancer stem cells, imputable to the diversity of the cell of origin, the heterogeneity and fluidity of the microenvironments, and a plethora of possible mutational events. Breast cancer stem cell targeting should hold a great promise for preventing metastasis, reducing the risk of drug resistance, and decreasing recurrence. However, only a few clinical trials assess the effectiveness of treatments on this specific cancer cell population. Additional considerations for the targeting of breast cancer stem cells need to be given to the tumor microenvironment. It is known to promote self-renewal, plasticity, and resistance to treatments. The fate of breast cancer stem cells is indissociable from its environment.

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Cellular, transcriptomic and isoform heterogeneity of breast cancer cell line revealed by full-length single-cell RNA sequencing

Cited by 28 publications

References 70 publications

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Current Achievements and Applications of Transcriptomics in Personalized Cancer Medicine

Breast cancers, mammary stem cells, and cancer stem cells, characteristics, and hypotheses

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