Origin and interpretation of cancer transcriptome profiling: the essential role of the stroma in determining prognosis and drug resistance

Goossens, Nicolas; Hoshida, Yujin; Aguirre‐Ghiso, Julio A.

doi:10.15252/emmm.201505284

Cited by 6 publications

(6 citation statements)

References 14 publications

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“…In addition to CTCs, the hybrid E/M phenotype was also observed in primary human cancers including prostate cancer, breast cancer, and lung cancer [21][22][23][24]. However, the EMT statue of human cancers was mostly characterized by the bulk tumor transcriptomes, and recent evidence indicates that the mesenchymal gene expression of the hybrid E/M status may likely be originated from the stromal cells in and around the tumors [25]. Single-cell RNA sequencing was used to distinguish the mesenchymal transcriptomes between stromal cells and EMT tumor cells.…”

Section: Evidence Of Hybrid E/m In Cancersmentioning

confidence: 99%

Hybrid Epithelial/Mesenchymal State in Cancer Metastasis: Clinical Significance and Regulatory Mechanisms

Liao

Yang

2020

Cells

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Epithelial-mesenchymal transition (EMT) has been well recognized for its essential role in cancer progression as well as normal tissue development. In cancer cells, activation of EMT permits the cells to acquire migratory and invasive abilities and stem-like properties. However, simple categorization of cancer cells into epithelial and mesenchymal phenotypes misleads the understanding of the complicated metastatic process, and contradictory results from different studies also indicate the limitation of application of EMT theory in cancer metastasis. Nowadays, growing evidence suggests the existence of an intermediate status between epithelial and mesenchymal phenotypes, i.e., the “hybrid epithelial-mesenchymal (hybrid E/M)” state, provides a possible explanation for those conflicting results. Appearance of hybrid E/M phenotype offers a more plastic status for cancer cells to adapt the stressful environment for proceeding metastasis. In this article, we review the biological importance of the dynamic changes between the epithelial and the mesenchymal states. The regulatory mechanisms encompassing the translational, post-translational, and epigenetic control for this complex and plastic status are also discussed.

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Section: Evidence Of Hybrid E/m In Cancersmentioning

confidence: 99%

Hybrid Epithelial/Mesenchymal State in Cancer Metastasis: Clinical Significance and Regulatory Mechanisms

Liao

Yang

2020

Cells

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“…In case of advanced cancers, CTCs frequently exhibit pronounced hybrid E/M phenotypes and collective migration of cells [ 8 ]. Partial EMT features are also evidenced from M gene expression of the stromal cells around the primary tumours [ 79 ] of breast, lung and prostate [ 8 ]. In HNSCC, the leading edge of primary tumours elicits partial EMT features and helps in determining nodal metastasis.…”

Section: Preclinical and Clinical Evidence Of Hybrid Emtmentioning

confidence: 99%

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

et al. 2020

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Epithelial mesenchymal transition (EMT) is a complex process through which epithelial (E) cells lose their adherens junctions, transform into mesenchymal (M) cells and attain motility, leading to metastasis at distant organs. Nowadays, the concept of EMT has shifted from a binary phase of interconversion of pure E to M cells and vice versa to a spectrum of E/M transition states preferably coined as hybrid/partial/intermediate EMT. Hybrid EMT, being a plastic transient state, harbours cells which co-express both E and M markers and exhibit high tumourigenic properties, leading to stemness, metastasis, and therapy resistance. Several preclinical and clinical studies provided the evidence of co-existence of E/M phenotypes. Regulators including transcription factors, epigenetic regulators and phenotypic stability factors (PSFs) help in maintaining the hybrid state. Computational and bioinformatics approaches may be excellent for identifying new factors or combinations of regulatory elements that govern the different EMT transition states. Therapeutic intervention against hybrid E/M cells, though few, may evolve as a rational strategy against metastasis and drug resistance. This review has attempted to present the recent advancements on the concept and regulation of the process of hybrid EMT which generates hybrid E/M phenotypes, evidence of intermediate EMT in both preclinical and clinical setup, impact of partial EMT on promoting tumourigenesis, and future strategies which might be adapted to tackle this phenomenon.

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“…Aforementioned data indicated conspicuous importance of TME not only in tumor development, but also in cancer recurrence and poor prognosis of patients. Moreover, it has been shown that expression of mesenchymal genes in tumor cells and mesenchymal signature in cancer transcriptome are related to aggressiveness of cancer [ 45 ]. Also, molecular profiling of stromal cells from various human tumors can provide significant diagnostic information [ 46 ].…”

Section: Mscs: Recruitment and Functions In Tmementioning

confidence: 99%

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

Trivanović

Krstić

Djordjević

et al. 2016

Mediators of Inflammation

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State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

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Origin and interpretation of cancer transcriptome profiling: the essential role of the stroma in determining prognosis and drug resistance

Cited by 6 publications

References 14 publications

Hybrid Epithelial/Mesenchymal State in Cancer Metastasis: Clinical Significance and Regulatory Mechanisms

Hybrid Epithelial/Mesenchymal State in Cancer Metastasis: Clinical Significance and Regulatory Mechanisms

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

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