SENP5 mediates breast cancer invasion via a TGFβRI SUMOylation cascade

Cashman, Rivki; Cohen, Helit; Ben‐Hamo, Rotem; Zilberberg, Alona; Efroni, Sol

doi:10.18632/oncotarget.1783

Cited by 35 publications

(33 citation statements)

References 48 publications

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“…Cancer type Deregulation References oral Overexpression of SENP3 Overexpression of SENP5 [139][140][141] breast Low expression of SENP5 contributes to better survival [142] Downregulation of SENP6 [143] USPL1 breast Expression contributes to risk of Grade 3 breast tumors [144] …”

Section: Proteinsmentioning

confidence: 99%

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

Eifler

Vertegaal

2015

Trends in Biochemical Sciences

245

211

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SUMOylation plays critical roles during cell cycle progression. Many important cell cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via SUMOylation. The dynamic SUMOylation pattern observed throughout the cell cycle is ensured via distinct spatial and temporal regulation of the SUMO machinery. Additionally, SUMOylation cooperates with other post-translational modifications to mediate cell cycle progression. Deregulation of these SUMOylation and deSUMOylation enzymes causes severe defects in cell proliferation and genome stability. Different types of cancers were recently shown to be dependent on a functioning SUMOylation system, a finding that could potentially be exploited in anti-cancer therapies. KeywordsSUMO; mitosis; SUMOylation; cancer; cell cycle SUMO: a ubiquitin-like modifier that regulates nuclear processesThe complexity of eukaryotic proteomes is widely expanded by protein processing and a vast array of posttranslational modifications. The quick and reversible attachment of small modifiers is essential for all cellular processes and ensures dynamic and rapid responses to extracellular and intracellular stimuli. Apart from chemical modifications such as phosphorylation [1], glycosylation [2] and acetylation [3], small polypeptides can be attached to proteins, resulting in a change in the activity, localization, half-life or interactome of the target protein. Since the initial discovery of ubiquitin, the founding member of these small protein posttranslational modifications in 1975 [4], a large family of structurally related ubiquitin-like modifiers has been uncovered including SUMO, Nedd8, ISG15, FAT10, FUB1, UFM1, URM1, Atg12 and Atg8 [5][6][7][8]. The attachment of these small ubiquitin-like modifiers is catalysed by an enzymatic cascade consisting of an activating enzyme (E1), a conjugating enzyme (E2) and a ligase (E3), and can be reversed by specific and cell cycle control. It is therefore not surprising that SUMO signal transduction has been implicated in the development of several different cancer types, which could potentially be exploited in anti-cancer therapies. In this review we will focus on the role of SUMO in cell cycle regulation, specifically highlighting its physiological relevance and its deregulation in cancer. Recent progress includes the identification of many novel SUMO substrates with important roles in cell cycle progression using proteomic approaches, and the demonstration that different mouse cancer models are dependent on a functioning SUMOylation system. Switching of SUMOylation in these cancer models caused a proliferation block of the cancer cells, showing that SUMO conjugating enzymes are potential drug targets. Europe PMC Funders Group Twenty years of SUMO research in cell cycle controlSUMO was linked to cell cycle progression even before the identification of the small protein modifier itself. Twenty years ago, the yeast SUMO conjugating enzyme Ubc9 was first proposed to be a ubiquitin conjugating enzyme. Ubc9 was s...

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Section: Proteinsmentioning

confidence: 99%

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

Eifler

Vertegaal

2015

Trends in Biochemical Sciences

245

211

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“…Oral squamous cell carcinoma Diagnosis [92] Breast Prognosis [93] SENP6 Breast Diagnosis [94] SENP7 Breast Diagnosis [95] USPL1 Breast Risk assessment [96] SUMO1, SUMO2/3 Astrocytic brain Diagnosis, progression [60] SUMO1 Hepatocellular carcinoma Diagnosis [97] Lip Diagnosis [98] Oral squamous cell carcinoma Diagnosis, prognosis [99] AML: Acute myeloid leukemia; MDS: Myelodysplastic syndrome.…”

Section: Senp5mentioning

confidence: 99%

“…Furthermore, using bioinformatics analysis of published microarray data, SENP5 expression levels stratified breast cancer patients into two survival groups: those with low SENP5 were associated with better prognosis and higher survival [93] compared with the high-expressing REviEW Mattoscio & Chiocca future science group SENP5 patients. Mechanistically, SENP5 promoted proliferation, migration and invasion of breast cancer cells probably by modulating the TGF-βRI/MMP9 axis.…”

Section: Sumo Proteasesmentioning

confidence: 99%

SUMO pathway components as possible cancer biomarkers

Mattoscio

Chiocca

2015

Future Oncol.

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SUMOylation is a key post-translational modification that regulates crucial cellular functions and pathological processes. Recently, Small Ubiquitin-related MOdifier (SUMO) modification has emerged as a fundamental route that may drive different steps of human tumorigenesis. Indeed, alteration in expression or activity of one of the different SUMO pathway components may completely subvert cellular properties through fine-tuning modulation of protein(s) involved in carcinogenic pathways, leading to altered cell proliferation, apoptosis resistance and metastatic potential. Here we describe some of the most interesting findings pointing to a clear link between SUMO pathway and human malignancies. Importantly, a putative role for SUMO enzymes to predict cancer behavior can be speculated, and thus the possible application of alterations in SUMO pathway components as tumor biomarkers is discussed.

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“…Moreover, none of our 3q 19 genes overlaps with known gene signatures tested in this study, arguing a lack of efficacy of using these known gene signatures as prognostic factors in TNBC patients. Although the exact role of these 19 genes in breast cancer metastasis is unclear, 12 genes including FXR1 have been studied functionally or mechanistically in human cancers including lung and breast (Supplemental Table 21)919202122232425. For instance, PIK3CA is the most well-studied oncogene among our 3q gene signature due to its high mutation rate in human cancer, especially in breast cancer23.…”

Section: Discussionmentioning

confidence: 99%

A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy

Qian

Chen

et al. 2017

Sci Rep

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Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival. The 3q gene signature was strongly associated with lung metastasis only in TNBC (P < 0.0001, Hazard ratio (HR) 1.44, 95% confidence interval (CI), 1.31–1.60), significantly associated with brain but not bone metastasis regardless of TNBC status. The association of one 3q driver gene FXR1 with distant metastasis in TNBC (P = 0.01) was further validated by immunohistochemistry. In addition, the 3q gene signature was associated with better response to neoadjuvant chemotherapy in TNBC (P < 0.0001) but not in non-TNBC patients. Our study suggests that the 3q gene signature is a novel prognostic marker for lung and/or brain metastasis and a predictive marker for the response to neoadjuvant chemotherapy in TNBC, implying a potential role for 3q genes in the mechanism of organ-specific metastasis.

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SENP5 mediates breast cancer invasion via a TGFβRI SUMOylation cascade

Cited by 35 publications

References 48 publications

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

SUMO pathway components as possible cancer biomarkers

A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy

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