Early origin of cancer metastases: Dissemination and evolution of premalignant cells

Ansieau, Stéphane; Hinkal, George; Thomas, Clémence; Bastid, Jérémy; Puisieux, Alain

doi:10.4161/cc.7.23.7049

Cited by 20 publications

(12 citation statements)

References 64 publications

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“…While the SNAI1 and SNAI2 genes are reported to be frequently reactivated in numerous carcinomas (breast, esophageal, colon, kidney) [32]–[35], the status of the related SNAI3 gene has remained unclear. To address this question, SNAI3 expression was assessed by qRT-PCR in a cohort of primary human tumors (n = 44) encompassing four different carcinoma types (colon, lung, ESCC, kidney), as compared to healthy tissues or normal cell counterparts.…”

Section: Resultsmentioning

confidence: 99%

Snail Family Members Unequally Trigger EMT and Thereby Differ in Their Ability to Promote the Neoplastic Transformation of Mammary Epithelial Cells

et al. 2014

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By fostering cell commitment to the epithelial-to-mesenchymal transition (EMT), SNAIL proteins endow cells with motility, thereby favoring the metastatic spread of tumor cells. Whether the phenotypic change additionally facilitates tumor initiation has never been addressed. Here we demonstrate that when a SNAIL protein is ectopically produced in non-transformed mammary epithelial cells, the cells are protected from anoikis and proliferate under low-adherence conditions: a hallmark of cancer cells. The three SNAIL proteins show unequal oncogenic potential, strictly correlating with their ability to promote EMT. SNAIL3 especially behaves as a poor EMT-inducer comforting the concept that the transcription factor functionally diverges from its two related proteins.

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Section: Resultsmentioning

confidence: 99%

Snail Family Members Unequally Trigger EMT and Thereby Differ in Their Ability to Promote the Neoplastic Transformation of Mammary Epithelial Cells

et al. 2014

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“…Recent emerging theory of early metastasis model indicated that metastatic-prone cancer cells might leave the primary tumor site much earlier than canonical theory of late stages tumor metastasis model (44). The colonized and expanded cancer cells from early metastasis could confer additional changes and become heterogeneous compared with cancer cells in primary tumor site.…”

Section: Discussionmentioning

confidence: 99%

HDAC Inhibitors Augmented Cell Migration and Metastasis through Induction of PKCs Leading to Identification of Low Toxicity Modalities for Combination Cancer Therapy

Lin

Wang

Chen

et al. 2012

Clinical Cancer Research

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Purpose: Histone deacetylase inhibitors (HDACi) are actively explored as new-generation epigenetic drugs but have low efficacy in cancer monotherapy. To reveal new mechanism for combination therapy, we show that HDACi induce cell death but simultaneously activate tumor-progressive genes to ruin therapeutic efficacy. Combined treatments to target tumorigenesis and HDACi-activated metastasis with low toxic modalities could develop new strategies for long-term cancer therapy.Experimental Design: Because metastasis is the major cause of cancer mortality, we measured cell migration activity and profiled metastasis-related gene expressions in HDACi-treated cancer cells. We developed low toxic combination modalities targeting tumorigenesis and HDACi-activated metastasis for preclinical therapies in mice.Results: We showed that cell migration activity was dramatically and dose dependently enhanced by various classes of HDACi treatments in 13 of 30 examined human breast, gastric, liver, and lung cancer cell lines. Tumor metastasis was also enhanced in HDACi-treated mice. HDACi treatments activated multiple PKCs and downstream substrates along with upregulated proapoptotic p21. For targeting tumorigenesis and metastasis with immediate clinical impact, we showed that new modalities of HDACi combined drugs with PKC inhibitory agent, curcumin or tamoxifen, not only suppressed HDACi-activated tumor progressive proteins and cell migration in vitro but also inhibited tumor growth and metastasis in vivo.Conclusion: Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease.

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“…Therefore, reactivation of TWIST genes might simultaneously favor malignant conversion through the inhibition of Rb-and p53-dependent pathways and early cancer cell dissemination through EMT induction. It is noteworthy that the knock-down of the ZEB1, another embryonic transcription factor known to promote EMT, is also associated with senescence program induction , strengthening the link between EMT and senescence escape (Smit and Peeper, 2008;Ansieau et al, 2008b). Importantly, our laboratory and the Weinberg laboratory recently showed that EMT endows normal and transformed mammary epithelial cells with stemlike properties, including self-renewal capabilities Morel et al, 2008).…”

Section: Oncogenic and Pro-metastatic Potentials Of Twist Proteinsmentioning

confidence: 99%

TWISTing an embryonic transcription factor into an oncoprotein

et al. 2010

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Over the past decade, the reactivation of TWIST embryonic transcription factors has been described as a frequent event and a marker of poor prognosis in an impressive array of human cancers. Growing evidence now supports the premise that these cancers hijack TWIST's embryonic functions, granting oncogenic and metastatic properties. In this review, we report on the history and recent breakthroughs in understanding TWIST protein functions and the emerging role of the associated epithelialmesenchymal transition (EMT) in tumorigenesis. We then broaden the discussion to address the general contribution of reactivating embryonic programs in cancerogenesis.

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Early origin of cancer metastases: Dissemination and evolution of premalignant cells

Cited by 20 publications

References 64 publications

Snail Family Members Unequally Trigger EMT and Thereby Differ in Their Ability to Promote the Neoplastic Transformation of Mammary Epithelial Cells

Snail Family Members Unequally Trigger EMT and Thereby Differ in Their Ability to Promote the Neoplastic Transformation of Mammary Epithelial Cells

HDAC Inhibitors Augmented Cell Migration and Metastasis through Induction of PKCs Leading to Identification of Low Toxicity Modalities for Combination Cancer Therapy

TWISTing an embryonic transcription factor into an oncoprotein

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