Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Parrillas, Verónica; Martínez-Muñoz, Laura; Holgado, Borja L.; Kumar, Amit; Cascio, Graciela; Lucas, Pilar; Rodrı́guez-Frade, José Miguel; Malumbres, Marcos; Carrera, Ana C.; Wely, Karel H. M. van; Mellado, Mario

doi:10.1007/s00018-012-1145-8

Cited by 18 publications

(15 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our data, the overexpression of SOCS‐1 induced a decrease in the expression of anti‐apoptotic proteins, Mcl‐1 and Bcl‐xl, and significantly increased caspase‐3 activity in a dose‐dependent manner. In studies of cell cycle regulation, stable SOCS‐1‐transfected melanoma cells have been reported to lead to the G1/S transition defect, a secondary blockage in mitosis and accumulation of cells in the metaphase . Our study also shows that the overexpression of SOCS‐1 induced the G0/G1 arrest in G361 and SK‐MEL5 cells (Fig.…”

Section: Discussionsupporting

confidence: 69%

Suppressor of cytokine signalling‐1 induces significant preclinical antitumor effect in malignant melanoma cells

Tagami-Nagata

Serada

Fujimoto

et al. 2015

Experimental Dermatology

View full text Add to dashboard Cite

Malignant melanoma is the most aggressive form of skin cancer, responsible for the majority of skin cancer-related deaths. Metastatic melanoma is resistant to surgery, radiation or chemotherapy, and an effective therapy has not yet been established. Our study investigated the therapeutic potential of the suppressor of cytokine signalling-1 (SOCS-1), an endogenous inhibitor of the intracellular cytokine signalling pathway, for treating melanoma. Adenovirus vectors encoding the SOCS-1 gene were used to overexpress SOCS-1 in three melanoma cell lines (G361, SK-MEL5 and SK-MEL28). In G361 and SK-MEL5, overexpression of SOCS-1 significantly reduced cell proliferation and induced apoptosis in vitro and in vivo. Furthermore, we indicated that the antiproliferative effect of SOCS-1 correlated not only with decreased levels of the activation of signal transducer and activator of transcription (STAT)3 but also with increased levels of p53 expression and phosphorylation. These findings indicate the potential for clinical use of SOCS-1 for melanoma treatment.

show abstract

Section: Discussionsupporting

confidence: 69%

Suppressor of cytokine signalling‐1 induces significant preclinical antitumor effect in malignant melanoma cells

Tagami-Nagata

Serada

Fujimoto

et al. 2015

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…However, recent studies have demonstrated that SOCS1 could be directly implicated in tumor suppression by blocking mitosis in melanoma cell lines. In particular, SOCS1 was shown to reduce protein levels of G1 phase regulators of cell-cycle, such as cyclin D and cyclin E levels, and alters M phase protein levels through Cdh1 degradation [49]. Evidence of a direct role of SOCS3 in tumor progression in terms of disruption of cell cycle does not exist, likely due to the fact that SOCS3, differently from SOCS1, cannot localize in the cell nucleus, since it lacks of a nuclear translocation domain [50].…”

Section: Discussionmentioning

confidence: 99%

SOCS3 inhibits the pathological effects of IL-22 in non-melanoma skin tumor-derived keratinocytes

et al. 2017

View full text Add to dashboard Cite

Basal cell carcinomas (BCC) and squamous-cell carcinomas (SCC) are common malignancies in humans, caused by neoplastic transformation of keratinocytes of the basal or suprabasal layers of epidermis, respectively. Tumor-infiltrating lymphocytes (TILs) are frequently found in BCC and SCC, and functionally promote epithelial carcinogenesis. TILs secreting IL-22, in particular, participate to BCC and SCC growth by inducing keratinocyte proliferation and migration, as well as the expression of inflammatory, anti-apoptotic and pro-angiogenic genes.In this study, we identified SOCS3 as a valid candidate to be manipulated for suppressing tumorigenic functions in BCC and SCC. We found that SOCS3 and SOCS1 expression was reduced in vivo, in tumor lesions of BCC and SCC, as compared to other skin inflammatory conditions such as psoriasis, despite the high number of IL-22-secreting TILs. Moreover, IL-22 was not able to induce in vitro the transcriptional expression of SOCS3 in BCC-or SCC-derived keratinocytes, contrarily to healthy cells. Aimed at rescuing SOCS3 activity in these tumor contexts, a SOCS3-derived peptide, named KIR-ESS, was synthesized, and its ability in suppressing IL-22-induced responses was evaluated in healthy and transformed keratinocytes. We found that KIR-ESS peptide efficiently suppressed the IL-22 molecular signaling in keratinocytes, by acting on STAT3 and Erk1/2 cascade, as well as on the expression of STAT3-dependent downstream genes. Interestingly, after treatment with peptide, both healthy and transformed keratinocytes could no longer aberrantly proliferate and migrate in response to IL-22. Finally, treatment of athymic nude mice bearing SCC xenografts with KIR-ESS peptide concomitantly reduced tumor growth and activated STAT3 levels. As a whole, these data provides the rationale for the use in BCC and SCC skin tumors of SOCS3 mimetics, being able to inhibit the deleterious effects of IL-22 in these contexts.

show abstract

“…Adenovirus-mediated overexpression of SOCS1 can prevent HPV-related cells transformation by inducing degradation of the E7 oncoprotein 9 . SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome 103 . Enforced expression of SOCS1 leads to be resistant to transformation due to oncogenic induction 104 .…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

SOCS, inflammation, and cancer

et al. 2013

View full text Add to dashboard Cite

Signal transduction pathways elicited by cytokines and hormones have been shown to regulate distinct stages of development. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of cytokine signaling mediated by the JAK-STAT signaling pathway. In particular, SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers. Abnormal expression of SOCS1 and SOCS3 in cancer cells has been reported in human carcinoma associated with dysregulation of signals from cytokine receptors, Toll-like receptors (TLRs), and hormone receptors, resulting in malignancies. In this review, we focus on the role of SOCS1 and SOCS3 in cancer development. In addition, the potential of SOCS as a therapeutic target and diagnostic aid will be discussed.

show abstract

Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells

Cited by 18 publications

References 64 publications

Suppressor of cytokine signalling‐1 induces significant preclinical antitumor effect in malignant melanoma cells

Suppressor of cytokine signalling‐1 induces significant preclinical antitumor effect in malignant melanoma cells

SOCS3 inhibits the pathological effects of IL-22 in non-melanoma skin tumor-derived keratinocytes

SOCS, inflammation, and cancer

Contact Info

Product

Resources

About