Cancer cell plasticity: Impact on tumor progression and therapy response

Silva-Diz, Victoria da; Lorenzo-Sanz, Laura; Bernat-Peguera, Adrià; Lopez-Cerda, Marta; Muñoz, Purificacı́on

doi:10.1016/j.semcancer.2018.08.009

Cited by 155 publications

(135 citation statements)

References 198 publications

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“…Similarly, in glioblastoma, Suva et al, identified a core set of neurodevelopmental transcription factors (POU3F2, SOX2, SALL2, and OLIG2) that were sufficient to reprogram differentiated glioblastoma cells to CSCs (Suva, Rheinbay et al 2014). Tumor suppressor transcription factors like p53, pTEN has also been associated with CSC plasticity (Cabrera, Hollingsworth et al 2015, da Silva-Diz, Lorenzo-Sanz et al 2018, Santoro, Vlachou et al 2019. Loss of p53 lead to increased expression of Nestin and enable the dedifferentiation of hepatocytes and thereby contributes to cellular plasticity in liver carcinogenesis (Tschaharganeh, Xue et al 2014).…”

Section: Mechanisms Controlling Csc Plasticitymentioning

confidence: 99%

Cancer Stem Cell Plasticity – A Deadly Deal

Archana¹,

Kritika²,

Murali³

et al. 2019

Preprint

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Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

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Section: Mechanisms Controlling Csc Plasticitymentioning

confidence: 99%

Cancer Stem Cell Plasticity – A Deadly Deal

Archana¹,

Kritika²,

Murali³

et al. 2019

Preprint

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“…One important challenge in developing new therapeutic strategies is the dynamic and plastic behavior of tumor cells, especially of CSC. As it's well known, a central role in the regulation of cancer cell plasticity is played not only by genetic alterations, but also by epigenetic changes, including DNA methylation, histone modifications and non-coding RNA (ncRNA) activity [58] . By acting at transcriptional, posttranscriptional and translational level, ncRNAs represent key regulators of CSCs by modulating several biological processes including asymmetric division, unresponsiveness to treatments and EMT, thus affecting tumor progression and recurrence [58] .…”

Section: Conclusion and Clinical Implicationsmentioning

confidence: 99%

“…As it's well known, a central role in the regulation of cancer cell plasticity is played not only by genetic alterations, but also by epigenetic changes, including DNA methylation, histone modifications and non-coding RNA (ncRNA) activity [58] . By acting at transcriptional, posttranscriptional and translational level, ncRNAs represent key regulators of CSCs by modulating several biological processes including asymmetric division, unresponsiveness to treatments and EMT, thus affecting tumor progression and recurrence [58] . In addition, recent studies also suggest that similar to normal stem cells, CSCs seem to reside in specialized microenvironment ("CSC-niche") [46,50,70,172] , whose signals can support self-renewal and drug-resistance features and, thereby, may influence the plasticity of CSCs [173][174][175][176][177] .…”

Section: Conclusion and Clinical Implicationsmentioning

confidence: 99%

“…According with this theory, tumor cells represent a very plastic and dynamic population, with the ability to continuously shift between non-CSC and CSC states, in response to intrinsic and extrinsic stimuli. In this view, the stochastic and the CSC model not only are not mutually exclusive, but can be integrated with each other, adding a new level of tumor complexity [58] .…”

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confidence: 99%

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Stemness features in liver cancer

Correnti¹,

Booijink²,

Maira³

et al. 2018

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Heterogeneity is a cardinal hallmark of cancer, including primary liver cancer (PLC), and occurs at different layers including putative cell-of-origin. Current evidence suggests that within cellular subpopulations in PLC there are stem-like cells, the cancer stem cells (CSCs). The CSC concept has been recently proposed as an explanation of such intra-tumor heterogeneity. According to this model, CSCs are responsible for tumor initiation, recurrence, metastasis as well as drug-resistance. However, although the CSC hypothesis is intriguing and supported by a large number of experimental studies, there are still open questions regarding the origin of putative CSCs. Since chemoresistance and recurrence represent major issues in PLC treatment, the development of new therapeutic strategies is needed, for which a good understanding of tumor behavior and in particular of CSCs biology is an imperative prerequisite. In this review we summarize the regulatory pathways that support CSC features in PLC. Moreover, we highlight the key features of hepatic CSC, in terms of enhanced drug-resistance, increased metastatic potential and metabolic rearrangement. Knowledge of the molecular mechanisms underlying CSC biology may provide novel options for PLC combination therapies.Primary liver cancer (PLC) is one of the most common cancers worldwide and the second leading cause of cancer-related mortality [1,2] . The major forms of PLC comprise hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) [1,3-5] . HCC accounts for approximately 90% of all PLCs [1,3] , while CCA is the second most common form and accounts for about 5% of all PLCs [3][4][5] . HCC causes over 600,000 deaths worldwide annually, and its incidence and mortality are increasing at a fast rate [6-10] . On the other hand, CCA is characterized by a very poor prognosis, with a 5-years survival lower than 20%, and its incidence and worldwide mortality are also increasing [5,[11][12][13] . The high mortality rate of CCA may depend on its nonspecific or silent clinical features and the lack of specific markers that make it difficult to diagnose [14][15][16] .Many studies carried out in these last years have attempted to define which type of epithelial cell [hepatocytes, cholangiocytes, hepatic progenitor cells (HPCs) or all three] should be considered as the PLC cell of origin [17] . For a long time, HCC and CCA have been commonly accepted to derive from hepatocytes and cholangiocytes, respectively. Since mature hepatocytes and cholangiocytes have an enormous selfrenewal capacity and longevity, they meet the requirements to be targets for oncogenesis [17][18][19][20][21][22][23] . Detailed analyses of a wide range of PLC tumor types have reported that a rare form of combined HCC-CCA (cHCC-CCA) has intermediate characteristics between HCC and intrahepatic CCA (iCCA), suggesting that they could share the same stem/progenitor cell origin [18][19][20][21][22][23][24] . In this regard, since most PLCs arise on the background of chronic liver disease in the presence of an ex...

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“…Metastasis is highly complex, requiring cells to adapt to numerous different microenvironments as they leave the primary site, invade into and disseminate through the vasculature, seed at a distant site, and finally colonize and expand to form macrometastases (Gupta and Massague, 2006;Micalizzi et al, 2017;Smigiel et al, 2019). To navigate all the steps of the metastatic cascade, tumor cells likely require significant plasticity (da Silva-Diz et al, 2018;Chu et al, 2019;Smigiel et al, 2019;Yuan et al, 2019) (Figure 1). Plasticity can be defined as the ability of cells to toggle between different phenotypes without altering genotype, and is widely observed in embryonic differentiation, wound repair, and cancer metastasis .…”

Section: Introductionmentioning

confidence: 99%

Cellular Plasticity in Breast Cancer Progression and Therapy

Kong

Hughes

Ford

2020

Front. Mol. Biosci.

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With the exception of non-melanoma skin cancer, breast cancer is the most frequently diagnosed malignant disease among women, with the majority of mortality being attributable to metastatic disease. Thus, even with improved early screening and more targeted treatments which may enable better detection and control of early disease progression, metastatic disease remains a significant problem. While targeted therapies exist for breast cancer patients with particular subtypes of the disease (Her2+ and ER/PR+), even in these subtypes the therapies are often not efficacious once the patient's tumor metastasizes. Increases in stemness or epithelial-to-mesenchymal transition (EMT) in primary breast cancer cells lead to enhanced plasticity, enabling tumor progression, therapeutic resistance, and distant metastatic spread. Numerous signaling pathways, including MAPK, PI3K, STAT3, Wnt, Hedgehog, and Notch, amongst others, play a critical role in maintaining cell plasticity in breast cancer. Understanding the cellular and molecular mechanisms that regulate breast cancer cell plasticity is essential for understanding the biology of breast cancer progression and for developing novel and more effective therapeutic strategies for targeting metastatic disease. In this review we summarize relevant literature on mechanisms associated with breast cancer plasticity, tumor progression, and drug resistance.

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Cancer cell plasticity: Impact on tumor progression and therapy response

Cited by 155 publications

References 198 publications

Cancer Stem Cell Plasticity – A Deadly Deal

Cancer Stem Cell Plasticity – A Deadly Deal

Stemness features in liver cancer

Cellular Plasticity in Breast Cancer Progression and Therapy

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Cancer cell plasticity: Impact on tumor progression and therapy response

Cited by 155 publications

References 198 publications

Cancer Stem Cell Plasticity &ndash; A Deadly Deal

Cancer Stem Cell Plasticity &ndash; A Deadly Deal

Stemness features in liver cancer

Cellular Plasticity in Breast Cancer Progression and Therapy

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Cancer Stem Cell Plasticity – A Deadly Deal

Cancer Stem Cell Plasticity – A Deadly Deal