<i><scp>RARRES</scp>3</i> suppresses breast cancer lung metastasis by regulating adhesion and differentiation

Morales, M.L González; Arenas, Enrique J.; Urosevic, Jelena; Guiu, Marc; Fernández, Esther; Planet, Evarist; Fenwick, R. Bryn; Fernández-Ruiz, Sonia; Salvatella, Xavier; Reverter, David; Carracedo, Arkaitz; Massagué, Joan; Gomis, Roger R.

doi:10.15252/emmm.201303675

Cited by 69 publications

(72 citation statements)

References 63 publications

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“…34,35,38 In addition, the deregulation of Wnt/β-catenin signaling leads to abnormal cell proliferation and metastatic activity, which is frequently found in human breast cancer cells. In the present study, we demonstrate that RARRES3 exerts a remarkable effect on the acylation level of Wnt/β-catenin signaling molecules and therefore inhibits the tumorous growth and stemness properties of breast cancer cells.…”

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confidence: 99%

Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells

Hsu

Chan

et al. 2014

Cell Death Differ

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The Wnt/β-catenin signaling pathway has emerged as a key regulator of complex biological processes, such as embryonic development, cell proliferation, cell fate decision and tumorigenesis. Recent studies have shown that the deregulation of Wnt/β-catenin signaling is frequently observed and leads to abnormal cell growth in human breast cancer cells. In this study, we identified a novel regulatory mechanism of Wnt/β-catenin signaling through RARRES3 that targets and modulates the acylation status of Wnt proteins and co-receptor low-density lipoprotein receptor-related protein 6, resulting in the suppression of epithelialmesenchymal transition and cancer stem cell properties. Mutation of the conserved active site residues of RARRES3 indicates that RARRES3 serves as an acyl protein thioesterase that tethers its target proteins and modulates their acylation status. Furthermore, the functions of p53 in cell proliferation and Wnt/β-catenin signaling are significantly associated with the induction of RARRES3. Thus our findings provide a new insight into the molecular link between p53, protein acylation and Wnt/β-catenin signaling whereby RARRES3 plays a pivotal role in modulating the acylation status of signaling proteins.

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confidence: 99%

Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells

Hsu

Chan

et al. 2014

Cell Death Differ

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“…The use of MSK/EMC and Marseille cohorts were previously described2325. For MSK/EMC, MFS curves were plotted using Kaplan–Meier estimates and compared using the Gehan–Breslow–Wilcoxon test.…”

Section: Methodsmentioning

confidence: 99%

Stratification and therapeutic potential of PML in metastatic breast cancer

et al. 2016

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Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification.

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“…Mutation, epigenetic silencing, or reduced expression of luminal differentiation factors in the mammary gland (GATA3 and ELF5) has been shown to promote breast cancer metastasis (Kouros-Mehr et al 2008;Chakrabarti et al 2012). RARRES3, which is involved in retinoic acid-induced differentiation signaling, suppresses breast cancer lung metastasis initiation by promoting tumor differentiation (Morales et al 2014). In lung adenocarcinoma, the loss of NKX2-1, a lung lineage-specific transcription factor, increases metastatic seeding (Winslow et al 2011).…”

Section: Cell Fate Determinants As Regulators Of Micsmentioning

confidence: 99%

Distinctive properties of metastasis-initiating cells

2016

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Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming overt metastases. The tremendous rate of attrition during the process of metastasis implicates the existence of a rare and unique population of metastasis-initiating cells (MICs). MICs possess advantageous traits that may originate in the primary tumor but continue to evolve during dissemination and colonization, including cellular plasticity, metabolic reprogramming, the ability to enter and exit dormancy, resistance to apoptosis, immune evasion, and co-option of other tumor and stromal cells. Better understanding of the molecular and cellular hallmarks of MICs will facilitate the development and deployment of novel therapeutic strategies.

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RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation

Cited by 69 publications

References 63 publications

Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells

Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells

Stratification and therapeutic potential of PML in metastatic breast cancer

Distinctive properties of metastasis-initiating cells

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