SET domain containing protein 5 (SETD5) enhances tumor cell invasion and is associated with a poor prognosis in non-small cell lung cancer patients

Yu, Hairu; Sun, Jiayi; Zhao, Congxuan; Wang, Hao-Tian; Liu, Yeqiu; Xiong, Jiajia; Chang, Jing; Wang, Mixue; Wang, Wenhui; Ye, Dongman; Zhou, Haoming; Yu, Tao

doi:10.1186/s12885-019-5944-2

Cited by 17 publications

(19 citation statements)

References 39 publications

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“…Furthermore, higher SETD5 expression was associated with worse PPS in BC patients. SETD5 may be an oncogenic factor, as SETD5 was upregulated in non-small cell lung cancer and was a prognostic determinant in prior studies [19].…”

Section: Discussionmentioning

confidence: 97%

“…De novo heterozygous mutations in SETD5 are considered responsible for intellectual disability and autism spectrum disorders [17,18]. Overexpression of SETD5 is positively associated with poor prognosis in lung [19] and esophageal cancer [20]. A meta-analysis by Liu et al previously found that genetic alteration of histone lysine methyltransferases is closely linked to overall survival of BC patients [21].…”

Section: Introductionmentioning

confidence: 99%

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SETD5 Binding to EP300/HIF1α is Required for Glycolysis in Breast Cancer Stem-Like Cells

Yang

Zhang

et al. 2020

Preprint

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BackgroundGlycolysis plays a pivotal role in breast cancer stem-like cell reprogramming. The SET-domain containing 5 (SETD5) is a previously uncharacterized member of the histone lysine methyltransferase family. Yet, the molecular mechanisms underlying the promotion of stem-like and glycolysis activation traits of SETD5 have not been elucidated.MethodsBasing on public datasets, we explored clinicopathological and survival analysis of SETD5 on breast cancer (BC) patients. Spheroid formation, transfection experiments and measurement of glucose uptake and lactate production analyzed the regulatory function of SETD5 on glycolysis in breast cancer stem-like cells (BCSC). The impact of SETD5 on tumor growth was studied in a murine xenograft model. Immunohistochemistry, immunofluorescence, western blot, preparation of cytoplasmic and nuclear extracts and co-immunoprecipitation were used to determine the molecular mechanisms of SETD5 in cancer cell glycolysis.ResultsOur data displayed that overexpression of SETD5 in BC tissues is positively associated with progression. SETD5 overexpression is associated with poor post-progression survival in BC patients. SETD5 expression was enriched in spheroid cells. Downregulation of SETD5 significantly decreased BCSC properties and glycolysis in vitro and in vivo. Interestingly, SETD5 and glycolytic enzymes were accumulated in the central hypoxic regions of subcutaneous tumor tissues. Our mechanistic study found that SETD5 binding to EP300/hypoxia-inducible factor 1α (HIF1α) and work as an upstream effector. SETD5 knockdown reduced the expression of HIF1α, hexokinase-2, and 6-phosphofructo-2-kinase in the nucleus after treatment with cobalt chloride (CoCl2), a chemical hypoxia mimetic agent, which activates HIF1α to accumulate in the nucleus. ConclusionSETD5 is required for glycolysis in BCSCs through binding to EP300/HIF1α and could be a potential therapeutic target for BC patients.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

SETD5 Binding to EP300/HIF1α is Required for Glycolysis in Breast Cancer Stem-Like Cells

Yang

Zhang

et al. 2020

Preprint

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“…in an increased actin response in the interaction of breast cancer cells with natural killer cells 51 , in differential nuclear shape dynamics 52 , in the suppression of invasion 53 , and in cell fusion and the formation of cancer hybrid cells 54 . Other SETD proteins such as SETD5 have been associated with the invasion and migration of non-small cell lung cancer cells 55 . Interestingly, the authors found that SETD5 regulates the expression of master EMT transcription factors like Snail and ZO-1 55,56 .…”

Section: Discussionmentioning

confidence: 99%

“…Other SETD proteins such as SETD5 have been associated with the invasion and migration of non-small cell lung cancer cells 55 . Interestingly, the authors found that SETD5 regulates the expression of master EMT transcription factors like Snail and ZO-1 55,56 . They also found that higher SETD5 expression was significantly correlated with advanced TNM stage, lymph node metastasis, and overall survival rate.…”

Section: Discussionmentioning

confidence: 99%

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

Hassan

Rutsch

Győrffy

et al. 2020

Sci Rep

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In several carcinomas, the SET Domain Containing 3, Actin Histidine Methyltransferase (SETD3)is associated with oncogenesis. However, there is little knowledge about the role of SETD3 in the progression and prognosis of breast cancer. In this study, we first analyzed the prognostic value of SETD3 in breast cancer patients using the database of the public Kaplan-Meier plotter. Moreover, in vitro assays were performed to assess the role of SETD3 in the viability and capacity of invasion of human breast cancer cell lines. We observed that the high expression of SETD3 was associated with better relapse-free survival (RFS) of the whole collective of 3,951 patients, of Estrogen Receptorpositive, and of Luminal A-type breast cancer patients. However, in patients lacking expression of estrogen-, progesterone-and HER2-receptor, and those affected by a p53-mutation, SETD3 was associated with poor RFS. In vitro analysis showed that SETD3 siRNA depletion affects the viability of triple-negative cells as well as the cytoskeletal function and capacity of invasion of highly invasive MDA-MB-231 cells. Interestingly, SETD3 regulates the expression of other genes associated with cancer such as β-actin, FOXM1, FBXW7, Fascin, eNOS, and MMP-2. Our study suggests that SETD3 expression can act as a subtype-specific biomarker for breast cancer progression and prognosis.MTT proliferation assay. SETD3 depleted cells or controls (5 × 10 3 ) were plated in 96-well plates with DMEM medium (without phenol red) (Gibco ® , cat. No. 31053028, Germany) with FCS and incubated for 96 hours. After the incubation time, the medium was removed completely and cells were incubated with 20 µl/well of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) (cat. No. M2128-1G), at 5 mg/ml for 4 hours, at 37 °C. Subsequently, 100 µl of Stopping buffer, pH 4.7 composed of 10% (w/v) sodium dodecyl sulfate (SDS) (cat. No. 3599286) and 50% (v/v) N,) was added to stop the reaction and dissolve the formazan crystals. The absorbance was measured in a VersaMax ® Microplate Reader (Molecular Devices, Sunnyvale, CA, USA) at a wavelength of 595 nm. The proliferation of the control cells was defined as 100%. Results were derived from three independent sets of triplicate experiments. MTT, SDS, and N,N-Dimethyl formamide were from Sigma-

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“…The metastasis ability of malignant tumor cells is correlated with the phosphorylation levels of AKT(Ser473)and P38(Thr180/Tyr182)kinase [37].To confirm whether TGF-β1 could induce the increasing level of p-AKT(Ser473) and p-p38 (Thr180/Tyr182),we need the 5ng/μl TGF-β1 to stimulate 5-8F and HONE1 for 48h,Western Bolt was used to detect p-AKT(Ser473) and p-p38(Thr180/Tyr182) ( Figure.4).And the result demonstrated that TGF-β1 enhanced the expression of p-AKT(Ser473) and p-P38(Thr180/Tyr182).…”

Section: Tgf-β1 Promotes the Increasing Of P-akt And P-p38mentioning

confidence: 99%

The Role of P TEN Protein Phosphatase in Nasopharyngeal Carcinoma: The Ability of TGF-β1 Inducing Migration and Invasion was Inhibited by PTEN Protein Phosphatase through Down-regulating p-P38

Zhang

Wang

et al. 2020

Preprint

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BackgroundThe phosphatase and tensin homolog gene(PTEN) is a crucial cancersuppressor gene in nasopharyngeal carcinoma(NPC),which encodes the protein i-ncluding lipid phosphatase and protein phosphatase.p-P38 plays a vital role in the development process of cancers.However,whether and how PTEN protein p-hosphatase inhibit p-P38 expression and regulate migration and invasion in nas-opharyngeal carcinoma is still fully elucidated.MethodsThe abilities of migration and invasion were analyzed using Scratch,Transwell,Boyden experiments in NPC cells.Westere Blot was utilized to explo-re the expression of E-caherin,N-caherin and VIMENTIN in Epithelial-mesench-ymal transition(EMT),P38,p-P38(Thr180/Tyr182),AKT,p-AKT(Ser473),PTEN and its mutants.qPCR was done to detect the mRNA expression of PTEN and PTEN mutants.Immunofluorescence localization assay and Co-immunoprecipitatio-n assay was used to explore the mutual combination of PTEN and P38.ResultsWe verified that transforming growth factor-β1(TGF-β1) could induce migration,invasion,and EMT in NPC again,and appropriate concentration was 5ng/ml.Interesting,we demonstrated that 5ng/ml TGF-β1 enhanced the level of p-AKT(Ser473)and p-P38(Thr180/Tyr182).Further more,after overexpression of PTEN WT and various mutants including PTEN-C124S(lacking of both lipid p-hosphatase and protein phosphatase),PTEN-G129E(only lacking of lipid phosph-atase but remaining protein phosphatase),PTEN-Y138L(lacking of protein phosp-hatase but remaining lipid phosphatase),and PTEN 1-353(Lack of c-tail structur-e),we observed that PTEN protein phosphatase reduced the ability of migration,invasion by inhibiting TGF-β1-induced p-P38,but the PTEN c-tail did not invo-lvein this process.At last,we confirmed PTEN could bind to P38 each other.ConclusionsThe asssys in the study indicated that PTEN protein phosphatasemight be anticancer,where it was able to inhibit the ability of TGF-β1 inducingmigration and invasion by reducing p-P38 in NPC cells.

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SET domain containing protein 5 (SETD5) enhances tumor cell invasion and is associated with a poor prognosis in non-small cell lung cancer patients

Cited by 17 publications

References 39 publications

SETD5 Binding to EP300/HIF1α is Required for Glycolysis in Breast Cancer Stem-Like Cells

SETD5 Binding to EP300/HIF1α is Required for Glycolysis in Breast Cancer Stem-Like Cells

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

The Role of P TEN Protein Phosphatase in Nasopharyngeal Carcinoma: The Ability of TGF-β1 Inducing Migration and Invasion was Inhibited by PTEN Protein Phosphatase through Down-regulating p-P38

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SET domain containing protein 5 (SETD5) enhances tumor cell invasion and is associated with a poor prognosis in non-small cell lung cancer patients

Cited by 17 publications

References 39 publications

SETD5 Binding to EP300/HIF1α is Required for Glycolysis in Breast Cancer Stem-Like Cells

SETD5 Binding to EP300/HIF1α is Required for Glycolysis in Breast Cancer Stem-Like Cells

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

The Role of P TEN&nbsp;Protein Phosphatase&nbsp;in Nasopharyngeal Carcinoma: The Ability of TGF-β1&nbsp;Inducing Migration and Invasion was Inhibited by PTEN&nbsp;Protein Phosphatase&nbsp;through Down-regulating p-P38

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The Role of P TEN Protein Phosphatase in Nasopharyngeal Carcinoma: The Ability of TGF-β1 Inducing Migration and Invasion was Inhibited by PTEN Protein Phosphatase through Down-regulating p-P38