Cancer associated fibroblast: Mediators of tumorigenesis

Alexander, Jennifer I.; Cukierman, Edna

doi:10.1016/j.matbio.2020.05.004

Cited by 43 publications

(29 citation statements)

References 166 publications

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“…In addition to stress response, our findings indicated that ECM remodeling is a central task of metastasis-associated fibroblasts throughout the metastatic cascade. Indeed, ECM components and remodeling were demonstrated to facilitate breast cancer metastasis to lungs, and pancreatic cancer metastasis to liver ( Malanchi et al, 2012 ; Oskarsson et al, 2011 ; Nielsen et al, 2016 ; Cox et al, 2013 ; Yuzhalin et al, 2018 ; Alexander and Cukierman, 2020 ). We show that transcriptional rewiring of fibroblasts to mediate collagen synthesis and ECM organization is a central function of metastasis-associated fibroblasts, which is instigated early during the metastatic process and persists during advanced metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

Evolution of fibroblasts in the lung metastatic microenvironment is driven by stage-specific transcriptional plasticity

Shani

Raz

Monteran

et al. 2021

eLife

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Mortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. Cancer-associated fibroblasts (CAFs) are prominent players in the microenvironment of breast cancer. However, their role in the metastatic niche is largely unknown. In this study, we profiled the transcriptional co-evolution of lung fibroblasts isolated from transgenic mice at defined stage-specific time points of metastases formation. Employing multiple knowledge-based platforms of data analysis provided powerful insights on functional and temporal regulation of the transcriptome of fibroblasts. We demonstrate that fibroblasts in lung metastases are transcriptionally dynamic and plastic, and reveal stage-specific gene signatures that imply functional tasks, including extracellular matrix remodeling, stress response and shaping the inflammatory microenvironment. Furthermore, we identified Myc as a central regulator of fibroblast rewiring and found that stromal upregulation of Myc transcriptional networks is associated with disease progression in human breast cancer.

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Section: Discussionmentioning

confidence: 99%

Evolution of fibroblasts in the lung metastatic microenvironment is driven by stage-specific transcriptional plasticity

Shani

Raz

Monteran

et al. 2021

eLife

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“…In addition to stress response, our findings indicated that ECM remodeling is a central task of metastases-associated fibroblasts throughout the metastatic cascade. Indeed, ECM components and remodeling were demonstrated to facilitate breast cancer metastasis to lungs, and pancreatic cancer metastasis to liver 13,14,16,[53][54][55] . We show that transcriptional rewiring of fibroblasts to mediate tasks such as collagen synthesis and ECM organization is a central function of metastases-associated fibroblasts, which is instigated early during the metastatic process and persists during advanced metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

Evolution of metastases-associated fibroblasts in the lung microenvironment is driven by stage-specific transcriptional plasticity

Shani

Raz

Megides

et al. 2019

Preprint

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Running Title: Evolution of metastases-associated fibroblasts SummaryMortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. Cancer-associated fibroblasts (CAFs) are prominent players in the microenvironment of breast cancer. However, their role in the metastatic niche is largely unknown. In this study, we profiled the transcriptional co-evolution of lung fibroblasts isolated from transgenic mice at defined stage-specific time points of metastases formation. Employing multiple knowledge-based platforms of data analysis provided powerful insights on functional and temporal regulation of the transcriptome of fibroblasts. We demonstrate that fibroblasts in lung metastases are transcriptionally dynamic and plastic, and reveal stage-specific gene signatures that imply functional tasks, including extracellular matrix remodeling, stress response and shaping the inflammatory microenvironment. Furthermore, we identified Myc as a central regulator of fibroblast rewiring and found that stromal upregulation of Myc transcriptional networks is associated with worse survival in human breast cancer.

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“…Thus, cancer matrix remodelling consists of a juxtaposition of processes: stromal cell recruitment and proliferation leads to excessive deposition of large ECM components such as collagens and proteoglycans, while the simultaneous breakdown of ECM elements from cancer cell-derived secretory factors allows for BM degradation and the process of invasion to be initiated. ECM provides both biochemical and biomechanical cues to promote cancer 93 – 95 . The ECM can directly influence tumour cells but also indirectly promote angiogenesis, inflammation, and further stromal activation 73 , 76 , 93 , 96 .…”

Section: The Cancer Cell Secretome Activates the Tumour Microenvironmmentioning

confidence: 99%

The cancer cell secretome drives cooperative manipulation of the tumour microenvironment to accelerate tumourigenesis

Ritchie

Reed

Pereira

et al. 2021

Fac Rev

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Cellular secretions are a fundamental aspect of cell–cell and cell–matrix interactions in vivo . In malignancy, cancer cells have an aberrant secretome compared to their non-malignant counterparts, termed the “cancer cell secretome”. The cancer cell secretome can influence every stage of the tumourigenic cascade. At the primary site, cancer cells can secrete a multitude of factors that facilitate invasion into surrounding tissue, allowing interaction with the local tumour microenvironment (TME), driving tumour development and progression. In more advanced disease, the cancer cell secretome can be involved in extravasation and metastasis, including metastatic organotropism, pre-metastatic niche (PMN) preparation, and metastatic outgrowth. In this review, we will explore the latest advances in the field of cancer cell secretions, including its dynamic and complex role in activating the TME and potentiating invasion and metastasis, with comments on how these secretions may also promote therapy resistance.

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Cancer associated fibroblast: Mediators of tumorigenesis

Cited by 43 publications

References 166 publications

Evolution of fibroblasts in the lung metastatic microenvironment is driven by stage-specific transcriptional plasticity

Evolution of fibroblasts in the lung metastatic microenvironment is driven by stage-specific transcriptional plasticity

Evolution of metastases-associated fibroblasts in the lung microenvironment is driven by stage-specific transcriptional plasticity

The cancer cell secretome drives cooperative manipulation of the tumour microenvironment to accelerate tumourigenesis

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