Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer

Sasi, Walid; Jiang, Wen Guo; Sharma, Anup; Mokbel, Kefah

doi:10.1186/1471-2407-10-178

Cited by 93 publications

(109 citation statements)

References 49 publications

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“…Expression of SOCS family proteins has been reported to be deregulated in many cancers (Table 3). For example, higher SOCS 1, 3, 4 and 7 expression levels were associated with earlier tumor stage and better clinical outcome in breast cancer [77,78]. The expression of SOCS1 is absence in normal skin or melanocytic nevi while up-regulated in melanoma and related to tumor invasion as well as stage of the disease indicating that SOCS1 has prognostic significance in melanoma [79].…”

Section: Socs Proteins In Rtk Regulated Diseasesmentioning

confidence: 99%

SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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SOCS proteins in regulation of receptor tyrosine kinase signaling.Uddin, Kazi; Kabir, Nuzhat N; Flores-Morales, Amilcar; Rönnstrand, Lars Link to publication Citation for published version (APA): Kazi, J. U., Kabir, N. N., Flores-Morales, A., & Rönnstrand, L. (2014). SOCS proteins in regulation of receptor tyrosine kinase signaling. Cellular and Molecular Life Sciences, 71(17), 3297-3310. DOI: 10.1007/s00018-014-1619-y General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractThe receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many of this family of kinases are overexpressed or mutated in human malignancies and thus became attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressor of cytokine signaling (SOCS) family proteins are well known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7 and CIS. A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs sometimes can bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways.

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Section: Socs Proteins In Rtk Regulated Diseasesmentioning

confidence: 99%

SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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“…Thus, there might be different mechanisms involved in the interactions between SOCS1 and signal transmission pathways. However, contradictory results reported by Sasi et al (2010) in breast cancer. They demonstrated higher SOCS1 and SOCS3 transcript level among women who remained disease free compared to those who developed local recurrence and OS in breast cancer.…”

Section: Discussionmentioning

confidence: 70%

“…In head and heck cell lines, Rossa et al (2012) observed decreased SOCS3 expression in early stage cancer cells which was similar to our results. The contradictory findings was shown in breast cancer by Sasi et al (2010) with decreased SOCS1 mRNA expression with increasing TNM staging but they have not found significant association with grade of tumors. Also, in gastric cancer, loss of SOCS1 may be involved in lymph node metastasis and tumor progression (Oshimo et al, 2004), while restoration of its expression suppressed development and progression of hepatocellular carcinoma cells was observed (Wu et al, 2011).…”

Section: Discussionmentioning

confidence: 84%

“…Such as cutaneous T cell lymphoma, chronic myeloid leukemia, ALK+ anaplastic large cell lymphoma and some acute leukemia (Schuringa et al, 2000;Brender et al, 2001;Sakai et al, 2002;Cho-Vega et al, 2004;Roman-Gomaz et al, 2004). Also, in patients with colorectal cancer, papillary thyroid cancer, glioblastoma primary tissues, breast cancer and hepatocellular carcinoma tumors protein expression of SOCS1 and SOCS3 (Sasi et al, 2010;Wu et al, 2011;Ayyildiz et al, 2014;Kobawala et al, 2017). On the other hand, decreased SOCS1 and SOCS3 expression is observed in various cancers, including prostate cancer, hepatocellular carcinoma, laryngeal carcinoma, multiple myeloma, acute myeloid leukemia, pancreatic cancer and lymphoma (Mottok et al, 2009;Zhang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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Clinical Relevance of SOCS1 and SOCS3 in Patients with Oral Squamous Cell Carcinoma

Trivedi¹,

Kobawala²,

Ghosh³

et al. 2017

AJCRCO

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Though Suppressors of Cytokine Signaling (SOCS) proteins are known for negative feedback regulators of cytokine signaling their role in cancer is controversial. In the current study we sought to explore the occurrence of SOCS1 and SOCS3 in oral squamous cell carcinoma (OSCC) patients and evaluate their potential relationship with clinicopathological parameters and disease outcome. Using immunohistochemistry protein expression of SOCS1 and SOCS3 were evaluated from paraffin embedded primary OSCC tumors of 61 patients. Scoring was done by semiquantitative method. Cytoplasmic expression of SOCS1 and SOCS3 was noted in 54% and 59% of OSCC patients, respectively. Overexpression of SOCS1 was found to be significantly correlated with nodal status (p=0.020), disease stage (P = 0.014), histological grade (p=0.032) and lymphatic permeation (p=0.0001). SOCS3 showed significant association with nodal status (p=0.011), disease stage (p =0.009), lymphatic (p=0.0001) and vascular permeation (p=0.002). Kaplan-Meier curves for relapse-free survival (RFS) and overall survival (OS) demonstrated that SOCS3 remained significant indicator for predicting reduced RFS (Log rank=6.21, p=0.0127) and worse OS (Log rank=4.49, p=0.0340) for OSCC patients. However, in multivariate analysis it failed to reach at statistically significant. Our study found upregulated protein expression of SOCS1 and SOCS3 in advanced stage of OSCC patients having aggressive tumor phenotype. Therefore, study of SOCS1 and SOCS3 might be useful for precisely identifying high risk OSCC patients for more effective tailored treatment.

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“…Считается, что на уровень экспрессии SOCS1 мо-жет влиять микроокружение опухоли, продуцирующее опреде-ленные цитокины и гормоны [32,33].…”

Section: оа гаврилина и соавтunclassified