RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation

Kopparam, Jawahar; Chiffelle, Johanna; Angelino, Paolo; Piersigilli, Alessandra; Zangger, Nadine; Delorenzi, Mauro; Meylan, Etienne

doi:10.1038/cdd.2017.81

Cited by 27 publications

(28 citation statements)

References 54 publications

(53 reference statements)

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“…Thus, activation of STAT3 by RIP4 and subsequent changes in STAT3‐regulated genes may play a role in skin inflammation. It is reported that RIP4 hinders STAT3 activation in lung cancer cells, reducing cancer differentiation . These results seem to be quite different to our findings.…”

Section: Discussioncontrasting

confidence: 99%

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RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes

Bae

Jeong

Kim

et al. 2018

Experimental Dermatology

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The receptor-interacting protein kinase 4 (RIP4), a serine/threonine kinase, is an important modulator of epidermal growth and cutaneous inflammation. We found that RIP4 expression was significantly increased in the lesional skin of psoriasis. However, the role and regulatory mechanism of RIP4 in psoriasis have not been characterized. After treatment with IL-17, RIP4 mRNA and protein levels were increased in HaCaT cells. IL-17 also activated the RIP4 promoter. To understand the functional role of RIP4 in keratinocyte and to investigate the genes regulated by RIP4, RNA-based microarray analysis was performed. Among immune response-related genes, CCL20 expression was significantly changed by RIP4. To identify RIP4-interacting protein, an immunoprecipitation assay was performed. As a result, STAT3 was identified as a new protein that interacts with RIP4. The interaction of RIP4 and STAT3 enhanced STAT3 phosphorylation. In addition, the transcriptional activity of STAT3 induced by RIP4 regulated IL-17-mediated CCL20 expression in HaCaT cells. Taken together, these findings indicate that IL-17 increased RIP4-mediated STAT3 phosphorylation by directly interacting with STAT3. Thus, transcriptional activation of STAT3 promotes the expression of CCL20. Thus, activations of these signalling pathways by RIP4 may contribute to epithermal inflammation in psoriatic keratinocytes.

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Section: Discussioncontrasting

confidence: 99%

“…It is reported that RIP4 hinders STAT3 activation in lung cancer cells, reducing cancer differentiation. [46] These results seem to be quite different to our findings. In detail, STAT3 has two phosphorylation sites (tyrosine 705 and serine 727).…”

Section: Several Studies Have Reported Higher Levels Of Stat3contrasting

confidence: 99%

RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes

Bae

Jeong

Kim

et al. 2018

Experimental Dermatology

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“…Receptor-interacting serine/threonine protein kinase 4 (RIP4) is an ankyrin repeatcontaining kinase that is in charge of keratinocyte differentiation and delays cell migration during wound healing. It has recently been found to be a likely regulator of tumor differentiation in LUAD and contributes to epithelial identity and differentiation (22). This study demonstrated that poorly differentiated tumors correlate with low expression of RIP4, whereas high expression correlates with better overall survival.…”

Section: Stat3mentioning

confidence: 54%

“…Cells from their in vitro studies associate reduced RIP4 expression with elevated activation of STAT3 signaling and had an overall increased capacity for tissue invasion. In comparison, overexpression of RIP4 inhibited STAT3: after tail vein injections of RIP4overexpressing cells, tissue invasion and tumor formation were reduced, which was restored by co-expression of STAT3 (22).…”

Section: Stat3mentioning

confidence: 93%

Understanding the Complexity of the Tumor Microenvironment in K-ras Mutant Lung Cancer: Finding an Alternative Path to Prevention and Treatment

et al. 2020

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Kirsten rat sarcoma viral oncogene (K-ras) is a well-documented, frequently mutated gene in lung cancer. Since K-ras regulates numerous signaling pathways related to cell survival and proliferation, mutations in this gene are powerful drivers of tumorigenesis and confer prodigious survival advantages to developing tumors. These malignant cells dramatically alter their local tissue environment and in the process recruit a powerful ally: inflammation. Inflammation in the context of the tumor microenvironment can be described as either antitumor or protumor (i.e., aiding or restricting tumor progression, respectively). Many current treatments, like immune checkpoint blockade, seek to augment antitumor inflammation by alleviating inhibitory signaling in cytotoxic T cells; however, a burgeoning area of research is now focusing on ways to modulate and mitigate protumor inflammation. Here, we summarize the interplay of tumor-promoting inflammation and K-ras mutant lung cancer pathogenesis by exploring the cytokines, signaling pathways, and immune cells that mediate this process.

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“…STAT3 can regulate the growth cycle of cancer cells by affecting the expression of cyclin D1 and P27 [18]. Cyclin D1 and P27 are closely related to pathophysiological processes such as cell proliferation and apoptosis inhibition [19].…”

Section: Introductionmentioning

confidence: 99%

Erchen Plus Huiyanzhuyu Decoction Inhibits the Growth of Laryngeal Carcinoma in a Mouse Model of Phlegm‐Coagulation‐Blood‐Stasis Syndrome via the STAT3/Cyclin D1 Pathway

Tan

Luo

Zhou

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Erchen plus Huiyanzhuyu decoction (EHD), a Chinese herbal medicine (CHM) formula that consists of Erchen decoction and Huiyanzhuyu decoction, has achieved satisfactory results in the clinic. The main function of EHD is to remove phlegm and blood stasis, and EHD is suitable for phlegm-coagulation-blood-stasis (PCBS) syndrome in laryngeal cancer (LC). In this study, a xenograft mouse model of LC with PCBS syndrome was constructed by feeding a high-fat diet, swimming in ice water, and subcutaneously injecting epinephrine hydrochloride for 2 weeks. Based on the successful Chinese medicine syndrome model, Hep2-luciferase-GFP cells were injected subcutaneously under the armpit of the right upper limb in mice to form tumours. A mouse model of LC with PCBS syndrome was established via heterotopic transplantation. Then, the mice received intragastric administration of different concentrations of EHD daily, and cisplatin (DDP) was intraperitoneally injected every week for 21 days. Tumour fluorescence in mice was measured with a living animal imager on days 7, 14, 21, and 28 during treatment. The results of this experiment confirmed that a mouse model of Chinese medicine syndrome was successfully constructed. Moreover, EHD slowed the growth of xenograft tumours in nude mice; decreased the expression levels of STAT3, p-STAT3, and cyclin D1; and upregulated the expression level of P27. In brief, EHD inhibited laryngeal tumour growth in a xenograft mouse model of PCBS syndrome and regulated the STAT3/cyclin D1 signalling pathway. This study was the first to construct a Chinese medicine xenograft mouse model of LC with PCBS syndrome; in addition, this study clarified that EHD regulated the STAT3/cyclin D1 signalling pathway to inhibit the growth of LC and that EHD may be a promising novel therapeutic compound for the treatment of patients with LC.

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RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation

Cited by 27 publications

References 54 publications

RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes

RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes

Understanding the Complexity of the Tumor Microenvironment in K-ras Mutant Lung Cancer: Finding an Alternative Path to Prevention and Treatment

Erchen Plus Huiyanzhuyu Decoction Inhibits the Growth of Laryngeal Carcinoma in a Mouse Model of Phlegm‐Coagulation‐Blood‐Stasis Syndrome via the STAT3/Cyclin D1 Pathway

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