Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

Chanda, Ayan; Chan, Angela; Deng, Lili; Kornaga, Elizabeth; Enwere, Emeka K.; Morris, Donald G.; Bonni, Shirin

doi:10.1371/journal.pone.0177639

Cited by 37 publications

(44 citation statements)

References 42 publications

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“… 216 Moreover, sumoylation of SnoN by PIAS1 has an inhibitory effect on the invasive capacity of MDA-MB231 cells. 288 Particularly for SnoN, it has been reported that this protein regulates cell differentiation in normal skin and in benign skin tumors, but it promotes squamous cell carcinoma. 289 SnoN induces proliferation of ovarian cancer cells, whereas it promotes cell cycle arrest and senescence in non-transformed ovarian epithelial cells.…”

Section: Regulation Of Tgf-β/smad Signaling By Ski and Snonmentioning

confidence: 99%

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

Tecalco-Cruz

Ríos-López

Vázquez‐Victorio

et al. 2018

Sig Transduct Target Ther

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The transforming growth factor-β (TGF-β) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-β signaling pathway outcome relies on the control of the spatial and temporal expression of >500 genes, which depend on the functions of the Smad protein along with those of diverse modulators of this signaling pathway, such as transcriptional factors and cofactors. Ski (Sloan-Kettering Institute) and SnoN (Ski novel) are Smad-interacting proteins that negatively regulate the TGF-β signaling pathway by disrupting the formation of R-Smad/Smad4 complexes, as well as by inhibiting Smad association with the p300/CBP coactivators. The Ski and SnoN transcriptional cofactors recruit diverse corepressors and histone deacetylases to repress gene transcription. The TGF-β/Smad pathway and coregulators Ski and SnoN clearly regulate each other through several positive and negative feedback mechanisms. Thus, these cross-regulatory processes finely modify the TGF-β signaling outcome as they control the magnitude and duration of the TGF-β signals. As a result, any alteration in these regulatory mechanisms may lead to disease development. Therefore, the design of targeted therapies to exert tight control of the levels of negative modulators of the TGF-β pathway, such as Ski and SnoN, is critical to restore cell homeostasis under the specific pathological conditions in which these cofactors are deregulated, such as fibrosis and cancer.

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Section: Regulation Of Tgf-β/smad Signaling By Ski and Snonmentioning

confidence: 99%

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

Tecalco-Cruz

Ríos-López

Vázquez‐Victorio

et al. 2018

Sig Transduct Target Ther

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“…Overall, studies have revealed that each of PIAS1 and TIF1γ act via SnoN SUMOylation to suppress TGFβ-induced EMT in two-dimensional or three-dimensional culture systems [ 14 , 58 ] ( Figure 3 and Figure 4 ). Data also suggest that the PIAS1-SnoN SUMOylation axis suppresses TGFβ-induced invasive growth of 3D-breast cancer cell-derived organoid system [ 59 ] ( Figure 3 and Figure 4 ). Consistently, PIAS1 acts in a SUMO-E3 ligase-dependent manner to suppress the rate of breast-cancer cell-derived metastatic growth in a xenograft model [ 74 ].…”

Section: Sumoylation Of Tgfβ Pathway Signal Transducersmentioning

confidence: 99%

“…Consistently, PIAS1 acts in a SUMO-E3 ligase-dependent manner to suppress the rate of breast-cancer cell-derived metastatic growth in a xenograft model [ 74 ]. In order to promote EMT and invasive growth, data suggest that TGFβ, in turn, reduces the protein abundance of PIAS1 and proportion of SUMOylated SnoN in non-transformed mammary epithelial cells and breast carcinomas [ 14 , 59 ]. These data thus suggest the existence of an interplay between TGFβ signaling and PIAS1-SnoN SUMOylation axis in controlling EMT and potentially cancer invasion and metastasis.…”

Section: Sumoylation Of Tgfβ Pathway Signal Transducersmentioning

confidence: 99%

“…These data thus suggest the existence of an interplay between TGFβ signaling and PIAS1-SnoN SUMOylation axis in controlling EMT and potentially cancer invasion and metastasis. Interestingly, the protein abundance and nuclear localization of PIAS1 were found to predict positive outcome in a cohort of breast cancer patients suggesting potential utility of these two PIAS1 parameters as prognostic biomarkers in breast cancer [ 59 ]. In a tissue microarray (TMA) study, investigating the protein levels of TIF1γ and SnoN in tumor tissue derived from bladder cancer patients and as compared to surrounding normal tissue, a reduction in the protein abundance of only TIF1γ was found [ 84 ].…”

Section: Sumoylation Of Tgfβ Pathway Signal Transducersmentioning

confidence: 99%

“…SUMOylation is critical for the ability of SnoN to suppress TGFβ-induced EMT. In order to induce EMT, TGFβ signaling suppresses SnoN SUMOylation at least in part by increasing the protein turnover of its SUMO E3 ligase PIAS1 [ 14 , 58 , 59 ]. (6) SUMOylation regulates the activity of several EMT inducing transcription factors: TGFβ-induced expression of Snail, Slug, and Zeb2 contribute significantly to EMT induction.…”

Section: Figurementioning

confidence: 99%

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The SUMO System and TGFβ Signaling Interplay in Regulation of Epithelial-Mesenchymal Transition: Implications for Cancer Progression

Chanda

Sarkar

Bonni

2018

Cancers

Self Cite

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Protein post-translational modification by the small ubiquitin-like modifier (SUMO), or SUMOylation, can regulate the stability, subcellular localization or interactome of a protein substrate with key consequences for cellular processes including the Epithelial-Mesenchymal Transition (EMT). The secreted protein Transforming Growth Factor beta (TGFβ) is a potent inducer of EMT in development and homeostasis. Importantly, the ability of TGFβ to induce EMT has been implicated in promoting cancer invasion and metastasis, resistance to chemo/radio therapy, and maintenance of cancer stem cells. Interestingly, TGFβ-induced EMT and the SUMO system intersect with important implications for cancer formation and progression, and novel therapeutics identification.

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Breast Organotypic Cancer Models

Carranza-Rosales

Guzmán-Delgado

Carranza-Torres

et al. 2018

Current Topics in Microbiology and Immunology

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Breast cancer is the most common cancer type diagnosed in women, it represents a critical public health problem worldwide, with 1,671,149 estimated new cases and nearly 571,000 related deaths. Research on breast cancer has mainly been conducted using two-dimensional (2D) cell cultures and animal models. The usefulness of these models is reflected in the vast knowledge accumulated over the past decades. However, considering that animal models are three-dimensional (3D) in nature, the validity of the studies using 2D cell cultures has recently been questioned. Although animal models are important in cancer research, ethical questions arise about their use and usefulness as there is no clear predictivity of human disease outcome and they are very expensive and take too much time to obtain results. The poor performance or failure of most cancer drugs suggests that preclinical research on cancer has been based on an over-dependence on inadequate animal models. For these reasons, in the last few years development of alternative models has been prioritized to study human breast cancer behavior, while maintaining a 3D microenvironment, and to reduce the number of experiments conducted in animals. One way to achieve this is using organotypic cultures, which are being more frequently explored in cancer research because they mimic tissue architecture in vivo. These characteristics make organotypic cultures a valuable tool in cancer research as an alternative to replace animal models and for predicting risk assessment in humans. This chapter describes the cultures of multicellular spheroids, organoids, 3D bioreactors, and tumor slices, which are the most widely used organotypic models in breast cancer research.

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Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

Cited by 37 publications

References 42 publications

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

The SUMO System and TGFβ Signaling Interplay in Regulation of Epithelial-Mesenchymal Transition: Implications for Cancer Progression

Breast Organotypic Cancer Models

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