SOCS1 inhibits migration and invasion of prostate cancer cells, attenuates tumor growth and modulates the tumor stroma

Villalobos-Hernandez, Alberto; Bobbala, Diwakar; Kandhi, Rajani; Khan, Gulam Musawwir; Mayhue, Marian; Dubois, Claire M.; Ferbeyre, Gerardo; Saucier, Caroline; Ramanathan, Sheela; Ilangumaran, Subburaj

doi:10.1038/pcan.2016.50

Cited by 12 publications

(11 citation statements)

References 48 publications

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“…In STAT3 driven cancers, SOCS3 seems to be the most important negative feedback regulator and mouse models of SOCS3 ablation show strong STAT3 activation [119,121,122,123,124]. On the other hand, in solid cancers where STAT5 plays a causal role such as liver and prostate cancer, in addition to SOCS3, SOCS1 is frequently inactivated and mouse models of SOCS1 ablation increase both liver and prostate tumorigenesis [125,126,127,128,129,130,131,132]. In addition to their role as JAK/STAT signaling barriers, SOCS1 and SOCS3 can bind p53 and activate tumor suppressor responses such as senescence and ferroptosis when their expression is induced by aberrant STAT5 signaling in primary cells [133,134,135,136,137,138].…”

Section: Tumor Suppressor Functions and Negative Regulation Of Stamentioning

confidence: 99%

“…So far, the SOCS1-p53-senescence axis has been demonstrated in primary fibroblasts and mammary epithelial cells [133,139,140,141]. This mechanism may explain the better prognosis of some solid cancers with high p-STAT5 [142,143,144] and the high frequency of SOCS1 inactivation in STAT5-driven cancers [125,126,127,128,129,130,131,132]. However, it is difficult to obtain evidence of a senescence tumor-suppression response by studying established tumors that have already circumvented this pathway.…”

Section: Tumor Suppressor Functions and Negative Regulation Of Stamentioning

confidence: 99%

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STAT3 and STAT5 Activation in Solid Cancers

Igelmann

Neubauer

Ferbeyre

2019

Cancers

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The Signal Transducer and Activator of Transcription (STAT)3 and 5 proteins are activated by many cytokine receptors to regulate specific gene expression and mitochondrial functions. Their role in cancer is largely context-dependent as they can both act as oncogenes and tumor suppressors. We review here the role of STAT3/5 activation in solid cancers and summarize their association with survival in cancer patients. The molecular mechanisms that underpin the oncogenic activity of STAT3/5 signaling include the regulation of genes that control cell cycle and cell death. However, recent advances also highlight the critical role of STAT3/5 target genes mediating inflammation and stemness. In addition, STAT3 mitochondrial functions are required for transformation. On the other hand, several tumor suppressor pathways act on or are activated by STAT3/5 signaling, including tyrosine phosphatases, the sumo ligase Protein Inhibitor of Activated STAT3 (PIAS3), the E3 ubiquitin ligase TATA Element Modulatory Factor/Androgen Receptor-Coactivator of 160 kDa (TMF/ARA160), the miRNAs miR-124 and miR-1181, the Protein of alternative reading frame 19 (p19ARF)/p53 pathway and the Suppressor of Cytokine Signaling 1 and 3 (SOCS1/3) proteins. Cancer mutations and epigenetic alterations may alter the balance between pro-oncogenic and tumor suppressor activities associated with STAT3/5 signaling, explaining their context-dependent association with tumor progression both in human cancers and animal models.

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Section: Tumor Suppressor Functions and Negative Regulation Of Stamentioning

confidence: 99%

Section: Tumor Suppressor Functions and Negative Regulation Of Stamentioning

confidence: 99%

STAT3 and STAT5 Activation in Solid Cancers

Igelmann

Neubauer

Ferbeyre

2019

Cancers

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“…The SOCS family appears to be involved. SOCS1 caused significant reductions in wound closure and invasive behavior when it is stably expressed in prostate cancer cell lines [169]. In mouse models having metastatic tumors, none of the SOCS1-expressing mice had macro metastasis, unlike the controls, suggesting a role for SOCS1 in metastasis suppression.…”

Section: Jak/stat Signaling Promotes Cell Motility and Metastasismentioning

confidence: 99%

Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis

Trivedi

Starz‐Gaiano

2018

IJMS

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Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Despite immense information regarding Jak/STAT regulation, the signaling network has numerous missing links, which is slowing the progress towards developing drug therapies. In mammals, many components act in this cascade, with substantial cross-talk with other signaling pathways. In Drosophila, there are fewer pathway components, which has enabled significant discoveries regarding well-conserved regulatory mechanisms. Work across species illustrates the relevance of these regulators in humans. In this review, we showcase fundamental Jak/STAT regulation mechanisms in blood cells, stem cells, and cell motility. We examine the functional relevance of key conserved regulators from Drosophila to human cancer stem cells and metastasis. Finally, we spotlight less characterized regulators of Drosophila Jak/STAT signaling, which stand as promising candidates to be investigated in cancer biology. These comparisons illustrate the value of using Drosophila as a model for uncovering the roles of Jak/STAT signaling and the molecular means by which the pathway is controlled.

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“…In STAT3 driven cancers, SOCS3 seems to be the most important negative feedback regulator and mouse models of SOCS3 ablation show strong STAT3 activation [105,[107][108][109][110]. On the other hand, in solid cancers where STAT5 plays a causal role such as liver and prostate cancer, in addition to SOCS3, SOCS1 is frequently inactivated and mouse models of SOCS1 ablation increase both liver and prostate tumorigenesis [111][112][113][114][115][116][117][118]. In addition, SOCS1 and SOCS3 can bind p53 and activate tumor suppressor responses such as senescence and ferroptosis [119][120][121][122][123][124].…”

Section: The Suppressor Of Cytokine Signaling Socsmentioning

confidence: 99%

“…In addition, SOCS1 and SOCS3 can bind p53 and activate tumor suppressor responses such as senescence and ferroptosis [119][120][121][122][123][124]. STAT5 is a potent inducer of the SOCS1-p53-senescence axis and this may explain the better prognosis of cancers with high p-STAT5 [11,119,121,[125][126][127] and the high frequency of SOCS1 inactivation in STAT5-driven cancers [111][112][113][114][115][116][117][118].…”

Section: The Suppressor Of Cytokine Signaling Socsmentioning

confidence: 99%

STAT3 and STAT5 Activation in Solid Cancers

Igelmann¹,

Neubauer²,

Ferbeyre³

2019

Preprint

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The Signal Transducer and Activator of Transcription (STAT)3 and 5 are activated by many cytokine receptors to regulate specific gene expression and mitochondrial functions. Their role in cancer is largely context dependent as they can both act as oncogenes and tumor suppressors. We review here the role of STAT3/5 activation in solid cancers and summarize their association to survival in cancer patients. The molecular mechanisms that underpins the oncogenic activity of STAT3/5 signaling includes the regulation of genes that control cell cycle, cell death, inflammation and stemness. In addition, STAT3 mitochondrial functions are required for transformation. On the other hand, several tumor suppressor pathways act on or are activated by STAT3/5 signaling including the p19ARF/p53 pathway, tyrosine phosphatases, suppressor of cytokine signaling 1 and 3, the sumo ligase PIAS3, the E3 ubiquitin ligase TMF/ARA160 and the miRNAs miR-124 and miR-1181. Cancer mutations and epigenetic alterations may alter the balance between prooncogenic and tumor suppressor activities associated to STAT3/5 signaling explaining their context dependent association to tumor progression both in human cancers and animal models.

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SOCS1 inhibits migration and invasion of prostate cancer cells, attenuates tumor growth and modulates the tumor stroma

Abstract: Our findings support the tumor suppressor role of SOCS1 in PCa and suggest that attenuation of MET signaling is one of the underlying mechanisms. SOCS1 in PCa cells also appears to prevent the tumor-promoting functions of cancer-associated fibroblasts.

Cited by 12 publications

References 48 publications

STAT3 and STAT5 Activation in Solid Cancers

STAT3 and STAT5 Activation in Solid Cancers

Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis

STAT3 and STAT5 Activation in Solid Cancers

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