Ski: Double roles in cancers

Liao, Hai-Yang; Da, Chao-Ming; Wu, Zhi-Xi; Zhang, Haihong

doi:10.1016/j.clinbiochem.2020.10.015

Cited by 8 publications

(3 citation statements)

References 147 publications

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“…The protooncogene Ski is linked to various types of cancers as well as to human 1p36 syndrome and Shprintzen–Goldberg syndrome, which are characterized by severe central nervous system defects in addition to other symptoms [18, 20, 22, 23, 26]. Studies performed in normal and cancer cell lines show that Ski is a transcriptional regulator involved in numerous signaling and transcriptional networks, but most of the experiments were performed in vitro and using overexpression methods [17, 18]. To date, the knowledge about the physiological function of Ski in vivo is limited and discoveries of its molecular modes of action have been made primarily in the nervous system [18, 48, 49].…”

Section: Discussionmentioning

confidence: 99%

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The protooncogene Ski regulates the neuron-glia switch during development of the mammalian cerebral cortex

Grison

Karimaddini

Breda

et al. 2022

Preprint

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The brain is the most complex organ in mammals and understanding the origin of this complexity is a major challenge for developmental biologists. Crucial to the size and morphology of the cortex is the timing and transition of neural stem cell (NSC) fate. An interesting candidate for modulating and fine tuning these processes is the transcriptional regulator Ski, a protooncogene expressed in cortical cells. Ski is involved in diverse cellular processes and epigenetic programs, and mice deficient in Ski exhibit complex central nervous system defects that resemble some of the features observed in patients with 1p36 deletion syndrome and Shprintzen Goldberg syndrome. Here, we took advantage of in vivo transgenic labeling and next-generation sequencing to analyze the gene expression profiles of NSCs, basal progenitor (BP) cells, and newborn neurons (NBNs) from wildtype and Ski-deficient embryos throughout cortical development. We created a unique database that allowed us to identify and compare signaling pathways and transcriptional networks within each progenitor population in the presence and absence of Ski. We find that NSCs are the most affected cell population and uncover that mutant NSCs fail to switch to a gliogenic fate in time. We show that Ski functions in concert with the Bone Morphogenetic Protein (BMP) signaling pathway to alter the cell differentiation fate of NSCs from neurons to glia, which is key to generating adequate numbers of specific cell types during corticogenesis. Thus, by combining genetic tools and bioinformatic analysis, our work not only deepens the knowledge of how Ski functions in the brain, but also provides an immense resource for studying neurodevelopmental disorders.

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Section: Discussionmentioning

confidence: 99%

“…The transcriptional regulator Ski interacts with numerous intracellular proteins, thereby modulating gene regulation, signaling pathways, and epigenetic programs [17, 18]. However, hardly any of these functions have been tested under physiological conditions in vivo.…”

Section: Introductionmentioning

confidence: 99%

The protooncogene Ski regulates the neuron-glia switch during development of the mammalian cerebral cortex

Grison

Karimaddini

Breda

et al. 2022

Preprint

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“…In transgenic mice, muscle-specific expression of the Ski induces hypertrophy exclusively in a subset of fast muscle fibers (33). Even though SKI is usually upregulated in cancer and its knockdown decreases cell proliferation and migration, for example, in osteosarcoma cells, there are studies showing that SKI can be also considered as a tumor suppressor gene (34). For instance, SKI expression had inhibitory effects on the growth, migration, and tumor formation of lung cancer cells in vitro and in vivo, it also had good effects on the overall survival of patients with breast cancer (35,36).…”

Section: Discussionmentioning

confidence: 99%

Molecular Biomarkers of Response to Eribulin in Patients with Leiomyosarcoma

Woźniak

Boeckx

Modave

et al. 2021

Clinical Cancer Research

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Purpose: A randomized phase III study evaluated the efficacy of eribulin versus dacarbazine in patients with advanced liposarcoma and leiomyosarcoma. Improved overall survival (OS) led to approval of eribulin for liposarcoma, but not for leiomyosarcoma. Experimental Design: We explored the molecular profile of 77 archival leiomyosarcoma samples from this trial to identify potential predictive biomarkers, utilizing low-coverage whole-genome and whole-exome sequencing. Tumor molecular profiles were correlated with clinical data, and disease control was defined as complete/partial response or stable disease (RECIST v1.1). Results: Overall, 111 focal copy-number alterations were observed in leiomyosarcoma. Gain of chromosome 17q12 was the most common event, present in 43 of 77 cases (56%). In the eribulin-treated group, gains of 4q26, 20p12.2, 13q13.3, 8q22.2, and 8q13.2 and loss of 1q44 had a negative impact on progression-free survival (PFS), while loss of 2p12 correlated with better prognosis. Gains of 4q22.1 and losses of 3q14.2, 2q14.1, and 11q25 had a negative impact on OS in patients with leiomyosarcoma receiving eribulin. The most commonly mutated genes were TP53 (38%), MUC16 (32%), and ATRX (17%). The presence of ATRX mutations had a negative impact on PFS in both treatment arms; however, the correlation with worse OS was observed only in the eribulin-treated patients. TP53 mutations were associated with longer PFS on eribulin. Conclusions: Leiomyosarcoma has a complex genetic background, with multiple copy-number alterations and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of patients with leiomyosarcoma when treated with eribulin.

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SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration

Chen

Zhang

et al. 2022

Apoptosis

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Ski: Double roles in cancers

Cited by 8 publications

References 147 publications

The protooncogene Ski regulates the neuron-glia switch during development of the mammalian cerebral cortex

The protooncogene Ski regulates the neuron-glia switch during development of the mammalian cerebral cortex

Molecular Biomarkers of Response to Eribulin in Patients with Leiomyosarcoma

SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration

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