MLLT11/AF1q boosts oncogenic STAT3 activity through <i>Src</i>-PDGFR tyrosine kinase signaling

Park, Jino; Kim, Soojin; Joh, Joongho; Remick, Scot C.; Miller, Donald M.; Yan, Jun; Kanaan, Zeyad; Chao, Ju Hsien; Krem, Maxwell M.; Basu, Soumit; Hagiwara, Shotaro; Kenner, Lukas; Moriggl, Richard; Bunting, Kevin D.; Tse, William

doi:10.18632/oncotarget.9759

Cited by 27 publications

(40 citation statements)

References 48 publications

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“…Notably, PDGFR-β is known to induce STAT3 phosphorylation, and activated STAT3 leads to cell transformation [47,48]. Consequently, elevated STAT3 signaling inhibits apoptosis and supports cancer survival, producing a phenotype similar to chemo-resistance [49]. In the current study, sorafenib alone suppressed p-PDGFR-β and p-STAT3 levels as well as nuclear translocation of STAT3, and the combination treatment completely blocked the PDGFR-β/STAT3 signaling pathway ( Fig.…”

Section: Discussionsupporting

confidence: 52%

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Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-β/STAT3 Pathway

Fang¹,

Jung²,

Zhang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors with poor prognosis. Conventional chemotherapies including gemcitabine have failed owing to weak response and side effects. Hence novel treatment regimens are urgently needed to improve the therapeutic efficacy. In this study, we aimed to assess the anticancer activity of melatonin and sorafenib as a novel therapy against PDAC. Methods: We used various apoptosis assay and PDAC xenograft model to assess anticancer effect in vitro and in vivo. We applied phospho-receptor tyrosine kinase (RTK) array and phospho-tyrosine kinase array to explore the mechanism of the combined therapy. Western blotting, proximity ligation assay, and immunoprecipitation assay were also performed for validation. Results: Melatonin synergized with sorafenib to suppress the growth of PDAC both in vitro and in vivo. The effect was due to increased apoptosis rate of PDAC cells that was accompanied by mitochondria dysfunction. The enhanced anticancer efficacy by the co-treatment could be explained by blockade of PDGFR-β/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3. Conclusions: Melatonin reinforces the anticancer activity of sorafenib by downregulation of PDGFR-β/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3. The combination of the two agents might be a potential therapeutic strategy for treating PDAC.

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Section: Discussionsupporting

confidence: 52%

“…5 and 6). Considering the previous study that sorafenib suppresses STAT3 signaling associated with growth arrest and causes apoptosis [50], it seems that melatonin improves the anticancer activity of sorafenib through PDGFR-β/STAT3 pathway, and not the RAF/ MEK/ERK signaling pathway [49].…”

Section: Discussionmentioning

confidence: 96%

Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-β/STAT3 Pathway

Fang¹,

Jung²,

Zhang³

et al. 2018

Cell Physiol Biochem

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“…The binding of PDGF‐BB to PDGFR‐β activates several downstream signaling pathways . In particular, PDGF‐BB/PDGFR can stimulate Src and STAT3 expression. We investigated the potential for PDGF‐BB to act in an autocrine manner on CRC cells, and PDGF‐BB/Src/STAT3/VEGFA was identified as a signaling axis that may augment PDGF‐BB‐mediated promotion of colorectal cancer angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

Cheng

Jin

et al. 2019

Intl Journal of Cancer

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ETS transcription factors play important roles in tumor cell invasion, differentiation and angiogenesis. In this study, we initially demonstrated that ETS translocation variant 5 (ETV5) is abnormally upregulated in colorectal cancer (CRC), is positively correlated with CRC tumor size, lymphatic metastasis and tumor node metastasis (TNM) stage and indicates shorter survival and disease‐free survival in CRC patients. In vitro and in vivo experiments revealed that the downregulation of ETV5 could significantly suppress CRC cell proliferation. Moreover, overexpression of ETV5 could stimulate CRC angiogenesis in vitro and in vivo, which is consistent with RNA‐seq results. Then, we identified platelet‐derived growth factor BB (PDGF‐BB) as a direct target of ETV5 that plays an important role in ETV5‐mediated CRC angiogenesis through an angiogenesis antibody microarray. Additionally, PDGF‐BB could activate VEGFA expression via the PDGFR‐β/Src/STAT3 pathway in CRC cells and appeared to be positively correlated with ETV5 in CRC tissues. Finally, we revealed that ETV5 could bind directly to the promoter region of PDGF‐BB and regulate its expression through ChIP and luciferase assays. Overall, our study suggested that the transcription factor ETV5 could stimulate CRC malignancy and promote CRC angiogenesis by directly targeting PDGF‐BB. These findings suggest that EVT5 may be a potential new diagnostic and prognostic marker in CRC and that targeting ETV5 might be a potential therapeutic option for inhibiting CRC angiogenesis.

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Section: Resultsmentioning

confidence: 99%

“…The existing relationships between the new candidate genes mentioned in this section and other human cancers except for the lung cancer, were also mentioned in the sixth column of Table 1. 32,51,[57][58][59][60][61][62][63][64] The main source we used for this part was DisGeNET database. 68 Comparison of some associated diseases with the new candidate genes can help in selecting them to be checked experimentally to prove their association with the NSCLC.…”

Section: Candidate New Genes In Association With Nsclcmentioning

confidence: 99%

Considering smoking status, coexpression network analysis of non–small cell lung cancer at different cancer stages, exhibits important genes and pathways

Mortezaei

Tavallaei

Hosseini

2019

J of Cellular Biochemistry

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Non–small cell lung cancer (NSCLC) is the most common subtype of lung cancer among smokers, nonsmokers, women, and young individuals. Tobacco smoking and different stages of the NSCLC have important roles in cancer evolution and require different treatments. Existence of poorly effective therapeutic options for the NSCLC brings special attention to targeted therapies by considering genetic alterations. In this study, we used RNA‐Seq data to compare expression levels of RefSeq genes and to find some genes with similar expression levels. We utilized the “Weighted Gene Co‐expression Network Analysis” method for three different datasets to create coexpressed genetic modules having relations with the smoking status and different stages of the NSCLC. Our results indicate seven important genetic modules having important associations with the smoking status and cancer stages. Based on investigated genetic modules and their biological explanation, we then identified 13 newly candidate genes and 7 novel transcription factors in association with the NSCLC, the smoking status, and cancer stages. We then examined those results using other datasets and explained our results biologically to illustrate some important genes in relation with the smoking status and metastatic stage of the NSCLC that can bring some crucial information about cancer evolution. Our genetic findings also can be used as some therapeutic targets for different clinical conditions of the NSCLC.

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MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling

Cited by 27 publications

References 48 publications

Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-β/STAT3 Pathway

Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-β/STAT3 Pathway

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

Considering smoking status, coexpression network analysis of non–small cell lung cancer at different cancer stages, exhibits important genes and pathways

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