BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Ruige Yang,Xiangjing Fu,Jiangping Fan,Tingting Wang,Jian Song,Ting Xu,Yong Guo,Sai-Yang Zhang
Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC 50 value of 6.1 μmol/L, superior to the reference drug 5-fluorouracil (IC 50 : 9.63 ± 0.27 µmol/L). The structure–activity relationships (SARs) indicated that the introduction of –(4-NO 2 )Ph, 3-pyridyl, –(2-F)Ph, –(4-F)Ph, –(3-F)Ph, –(4-Cl)Ph, and –(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.
研究领域:
药理学
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肿瘤学
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分子生物学
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PubMed
高影响因子
Molecular Medicine Reports
·
2015
·Vol. 11
·期 6
·4101-4108
·
IF 1.554
Cheng Wang,Zi‑Man Zhu,Cheng‑Li Liu,Xiao‑Jun He,Hong‑Yi Zhang,Jia‑Hong Dong
The pathogenesis of hepatocellular carcinoma (HCC) is thought to involve the interaction of numerous genes. Identification of these genes and proteins which regulate liver carcinogenesis is critical for the exploration of novel targeted therapies. Yes‑associated protein (YAP) and large tumor suppressor 1 (LATS1) are associated with HCC cells. LATS1 is an upstream inhibitory factor of YAP in the Hippo pathway. The aim of the present study was to measure the expression of LATS1 in Yap‑downregulated cancer cells. Immunohistochemistry was used to determine YAP and LATS1 levels in HCC tissue samples. High YAP‑expressing cell lines were selected from two human hepatocellular carcinoma cells with different metastatic potential. In addition, changes in cell growth rates and LATS1 expression in human HCC 97H cells, in which YAP had been knocked down using RNA interference (RNAi). The proliferation of cells was evaluated using an MTS assay and changes in the progression of cell division were assessed through cell cycle analysis. Western blot analysis was then used to determine YAP and LATS1 expression levels in 97H cells. The results of the present study demonstrated that overexpression of YAP was negatively correlated with LATS1 expression in HCC cells (P=0.016). Knockdown of YAP using lentivirus‑small hairpin (sh)RNA significantly inhibited 97H cell growth; in addition, the downregulation of YAP protein levels (33.4%) was accompanied by downregulation of LATS1 protein levels (68.5%). In conclusion, these results demonstrated that as an inhibitor of YAP, LATS1 was decreased via downregulation of YAP using RNAi. This therefore indicated that the change in YAP levels in HCC cells may regulate LATS1 in a feedback manner.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Dantong Li,Jian Chen,Jiaqi An,Ying Gu,Zhikuo Dong,Xingxing Gao,Xiaoying Zhang,Yixin Zhang
Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely linked to intestinal mucosal microcirculatory dysfunction. Sweroside (SOS), a natural iridoid glycoside derived from plants such as Swertia mussotii , Swertia pseudochinensis , and Lonicera japonica , exhibits anti-inflammatory properties. Yet, its therapeutic potential and mechanisms in UC remain unexplored. This study aimed to investigate the effects of SOS on dextran sulfate sodium (DSS)-induced UC and its underlying mechanisms. Methods A DSS-induced UC mouse model was established to evaluate the efficacy of SOS. Inflammatory cytokine levels, intestinal barrier function (assessed via MUC2 immunofluorescence, FITC-dextran permeability, and tight junction protein analysis), and mucosal microcirculation (measured by Laser Speckle Contrast Imaging) were examined. Angiogenesis and endothelial cell (EC) damage were analyzed using ELISA, immunohistochemistry, and transmission electron microscopy. Transcriptomics and molecular docking were utilized to investigate SOS-mediated pathways, with subsequent validation by qRT-PCR, western blot, and immunofluorescence. Additionally, a cellular injury model was generated by treating human umbilical vein endothelial cells (HUVECs) with DSS. Cellular inflammatory and angiogenesis-related factors were quantified via ELISA, while migration and angiogenesis capabilities of HUVECs were assessed through scratch and tube-forming assays. The expression of the VEGF and Hippo pathway-related proteins was determined by western blot. Results SOS significantly ameliorated UC symptoms, reducing weight loss, diarrhea, and DAI scores while suppressing inflammatory infiltration and cytokine release. SOS enhanced intestinal barrier integrity via tight junction upregulation and improved microcirculation by attenuating EC injury and angiogenesis. Mechanistically, SOS regulated the VEGF and Hippo pathways, a key regulator of angiogenesis, as confirmed by transcriptomics and molecular docking. In vitro , SOS protected HUVECs from DSS-induced inflammation and angiogenesis, confirming the improvement of mucosal microcirculation by modulating VEGF and Hippo pathways. Conclusions SOS ameliorates DSS-induced UC by impacting the VEGF and Hippo pathways, thereby suppressing ECs' angiogenesis, restoring mucosal microcirculation, and mitigating intestinal inflammation. These findings highlight SOS as a promising therapeutic candidate for UC.
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PubMed
高影响因子
Postepy Dermatologii i Alergologii
·
2025
·Vol. 42
·期 4
·398-406
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IF 1.7
Bei Zhao,Yinghua Liu,Xuemei Tang,Shi Cheng
Introduction:The effectiveness of chemotherapy in treating melanoma is limited due to drug resistance. Previous studies have shown that SENP1 (Sentrin/SUMO-specific protease 1) is related to the tumour hypoxic microenvironment, tumorigenesis and metastasis.Aim:This study aimed to investigate its roles in drug resistance of melanoma.Material and methods:Originally, a concentration of 2 µg/ml dacarbazine (DTIC) was employed in the treatment of A375 and M14 cell lines for a duration of 24 h. Subsequently, the cells were transferred to fresh medium and allowed to proliferate until reaching 80% of their maximum density. This treatment cycle was then repeated for a total of 10 days, following which the DTIC concentration was doubled. The establishment of drug-resistant cell lines for both A375 and M14 occurred after 8 months of sustained and continuous treatment. The expression level of SENP1 was monitored monthly using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), with a fold change above 1.5 compared to the untreated condition considered as significant.Results:Finally, the study found that SENP1 was up-regulated by about 2.2-1.7 times in the drug-resistant cells. In addition, overexpression of SENP1 in normal A375 cells improved cell viability against DTIC. The study also found that Yes-associated protein (YAP) could form protein condensates in the cytoplasm while its expression was enhanced by SENP1-mediated deSUMOylation.Conclusions:This study suggests that there is a positive correlation between the ubiquitin-specific protease SENP1 and drug resistance in melanoma. Its up-regulation may lead to changes in the deSUMOylation of YAP, activate the Hippo signalling pathway, and increase the resistance of melanoma to DTIC.
研究领域:
癌症生物学
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分子生物学
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药理学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2022
·
IF 4.145
Xiaoxue Ma,Yiru Wang,Qi Liu,Baihe Han,Gang Wang,Ruoxi Zhang,Xingtao Huang,Xuedong Wang,Mengyue Yang,Chun Xing,Jingbo Hou,Bo Yu
Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC osteogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt-related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker α-smooth muscle actin (α-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.
研究领域:
心血管研究
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 6
·e0326978
·
IF 2.6
Chang Chen,Qiqi Yun,Juanli Ran,Ziyao Zhou,Pengxiang Zhang,Rong Li
Objective
This study investigated the interplay between Hippo-YAP and β-catenin signaling in regulating odontogenic differentiation of human dental pulp stem cells (DPSCs) and explored its potential implications for dentin-pulp regeneration.
Methods
Using lentivirus-mediated YAP overexpression/silencing, β-catenin siRNA knockdown, and pharmacological Wnt inhibition (via WIF-1), we assessed DPSC proliferation, migration, mineralization, and molecular markers (via qRT-PCR, immunofluorescence). In vivo validation employed subcutaneous transplantation of DPSC-seeded scaffolds in immunocompromised mice.
Results
YAP activation enhanced DPSC proliferation (1.44-fold), migration (1.39-fold), invasion (1.54-fold), and differentiation, as evidenced by elevated ALP activity (1.46-fold) and mineralization (1.36-fold). We observed transcriptional upregulation of odontogenic markers (RUNX2, DSPP, DMP1, OCN, ALP) and Wnt pathway components (β-catenin, Cyclin D1, c-Myc). Immunofluorescence revealed coordinated YAP and β-catenin expression patterns during differentiation. β-catenin silencing or Wnt inhibition abolished YAP-mediated functional enhancements and simultaneously suppressed YAP expression, partially confirming bidirectional regulation. In vivo , YAP-overexpressing DPSCs exhibited 1.27- to 1.62-fold induction of dentin-specific markers and β-catenin, whereas YAP silencing impaired these markers expression.
Conclusions
Our findings demonstrate that coordinated YAP and β-catenin signaling drives DPSC odontogenesis, with potential implications for dentin regeneration. Although reciprocal regulation is evident, direct molecular interactions require further validation.
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PubMed
高影响因子
Journal of Cell Communication and Signaling
·
2023
·
IF 4.1
Zhao Ye,Wang Huiling,He Tianhua,Ma Bo,Chen Guoguang,Tzeng Chimeng
Liver fibrosis is an aberrant wound healing response to tissue injury characterized by excessive extracellular matrix deposition and loss of normal liver architecture. Hepatic stellate cells (HSCs) activation is regards to be the major process in liver fibrogenesis which is dynamic and reversible. Both Hippo signaling core factor Yap and Hedgehog (Hh) signaling promote HSCs transdifferentiation thereby regulating the repair process of liver injury. However, the molecular function of YAP and the regulation between Yap and Hh during fibrogenesis remain uncertain. In this study, the essential roles of Yap in liver fibrosis were investigated. Yap was detected to be increased in liver fibrotic tissue by the thioacetamide (TAA)-induced zebrafish embryonic and adult models. Inhibition of Yap by both embryonic morpholino interference and adult’s inhibitor treatment was proved to alleviate TAA-induced liver lesions by and histology and gene expression examination. Transcriptomic analysis and gene expression detection showed that Yap and Hh signaling pathway have a cross talking upon TAA-induced liver fibrosis. In addition, TAA induction promoted the nuclear colocalization of YAP and Hh signaling factor GLI2α. This study demonstrates that Yap and Hh play synergistic protective roles in liver fibrotic response and provides new theoretical insight concerning the mechanisms of fibrosis progression. Graphical abstract
研究领域:
分子生物学
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肝病学
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细胞信号传导
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DOI
PubMed
高影响因子
Cell and Bioscience
·
2020
·Vol. 10
·期 1
·1-15
·
IF 5.026
Zhou Wei,Liu Meiyue,Li Xia,Zhang Peng,Li Jiong,Zhao Yue,Sun Guogui,Mao Weimin
Background Increased reactive oxygen species (ROS) production by arsenic treatment in solid tumors showed to be effective to sensitize cancer cells to chemotherapies. Arsenic nano compounds are known to increase the ROS production in solid tumors.Methods In this study we developed arsenic–ferrosoferric oxide conjugated Nano Complex (As2S2–Fe3O4, AFCNC) to further promote the ROS induction ability of arsenic reagent in solid tumors. We screen for the molecular pathways that are affect by arsenic treatment in ESCC cancer cells. And explored the underlying molecular mechanism for the arsenic mediated degradations of the key transcription factor we identified in the gene microarray screen. Mouse xenograft model were used to further verify the synthetic effects of AFCNC with chemo and radiation therapies, and the molecular target of arsenic treatment is verified with IHC analysis.Results With gene expression microarray analysis we found Hippo signaling pathway is specifically affected by arsenic treatment, and induced ubiquitination mediated degradation of YAP in KYSE-450 esophageal squamous cell carcinoma (ESCC) cells. Mechanistically we proved PML physically interacted with YAP, and arsenic induced degradation PML mediated the degradation of YAP in ESCC cells. As a cancer stem cell related transcription factor, YAP 5SA over expressions in cancer cells are correlated with resistance to chemo and radiation therapies. We found AFCNC treatment inhibited the increased invasion and migration ability of YAP 5SA overexpressing KYSE-450 cells. AFCNC treatment also effectively reversed protective effects of YAP 5SA overexpression against cisplatin induced apoptosis in KYSE-450 cells. Lastly, with ESCC mouse xenograft model we found AFCNC combined with cisplatin treatment or radiation therapy significantly reduced the tumor volumes in vivo in the xenograft ESCC tumors.Conclusion sTogether, these findings suggested besides ROS, YAP is a potential target for arsenic based therapy in ESCC, which should play an important role in the synthetic effects of arsenic nano complex with chemo and radiation therapy.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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纳米技术
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Hongyan Hai,Jingwen Mai,Jingyi Wang,Guangzhen Zheng,Changhui Liu
Ethnopharmacological relevance Cholestasis-induced liver diseases present with complex symptoms, exhibit significant individual variation in clinical treatment outcomes, and show diverse disease progression and prognoses, making them a key clinical focus in the field of hepatology. Zhizi Baipi Decoction (ZBP), derived from Treatise on Cold Damage Diseases, is used to treat jaundice. Composed of three Chinese herbal ingredients— Gardenia jasminoides J. Ellis, Phellodendron chinense C.K.Schneid., and Glycyrrhiza uralensis Fisch . ex DC., this formula has been confirmed to be effective against cholestatic liver disease by clinical studies; however, its active components and hepatoprotective mechanisms remain unclear. Aim of the study This study aimed to explore the therapeutic effects and underlying molecular mechanisms of ZBP and its key active ingredient liquiritin against cholestatic liver injury. Materials and methods A DDC diet-induced mouse model of cholestatic liver injury was established in this study. Multiple experimental approaches, including histopathological staining, ELISA, qPCR, Western blotting, 16 S rRNA gut microbiota sequencing, transcriptome sequencing, and LC-MS analysis, were applied to systematically evaluate the protective effects of ZBP and liquiritin on hepatic dysfunction, biliary injury, liver fibrosis, bile acid metabolic disorder, and gut microbiota dysbiosis. Molecular docking and cellular thermal shift assay (CETSA) were performed to verify the binding affinity between active components and core target proteins. In vivo and in vitro experiments were further conducted to validate the regulatory mechanisms. Results ZBP significantly ameliorated DDC-induced biliary lesions, hepatic inflammation, liver fibrosis, bile acid metabolic disturbance, and gut dysbiosis in cholestatic mice. Transcriptomic profiling combined with qPCR and Western blot validation identified the Hippo/YAP signaling pathway as the core regulatory axis responsible for ZBP-mediated hepatoprotection. LC-MS and molecular docking results indicated that liquiritin was a major bioactive component of ZBP with high binding affinity to key Hippo/YAP-related proteins. Further in vivo experiments demonstrated that liquiritin remarkably alleviated cholestasis-triggered biliary injury, hepatic inflammation, fibrosis, and abnormal bile acid metabolism. Consistently, in vivo tissue detection and in vitro cell experiments confirmed that liquiritin exerted protective effects against cholestatic liver damage by modulating the Hippo/YAP signaling pathway. Conclusion Collectively, ZBP and its major bioactive constituent liquiritin effectively ameliorate DDC-induced cholestatic liver injury via regulation of the Hippo/YAP signaling cascade. These findings provide novel experimental evidence and potential therapeutic targets for the clinical application of ZBP in the treatment of cholestatic liver diseases.
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高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2026
·Vol. 30
·期 17
·e71361
·
IF 4.7
Xin Ma,Yiting Huang,Xiao Lv,Xiumei Mo,Junfeng Liu,Fenggen Yan,Siqi Ye,Yu Zhang,Dacan Chen,Jinjing Jia
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and immune balance disorders. Currently, drugs for repairing the skin barrier in AD are limited. The gu-ben-hua-shi formula (AESS) has been shown to regulate Th1/Th2/Th17/Treg imbalance with good clinical effect. However, its effects on regulating autophagy, repairing the skin barrier, and interacting with Yes-associated protein (YAP) remain unknown. To elucidate the therapeutic effects of AESS on AD and to investigate its mechanism of restoring skin barrier function through the Hippo-YAP pathway. We conducted a single-arm observational study to evaluate the clinical efficacy of the AESS in patients with AD. Network pharmacology was used to predict the potential therapeutic targets and mechanisms. AD mouse models were established by house dust mite stimulation in Nishiki-nezumi Cinnamon/Nagoya mice, and the effects on autophagy and the skin barrier were measured using western blotting, immunofluorescence, mRFP-GFP-LC3 tandem fluorescence assay, and transmission electron microscopy. The effects of AESS serum on an AD-like inflammatory cell model were detected in HaCaT cells stimulated with interferon-γ (IFN-γ)/tumour necrosis factor-α (TNF-α). Activity of the Hippo-YAP signalling pathway was also investigated after YAP knockdown. AESS improved skin rash and barrier function, reduced eosinophil counts, and increased Th1/Th2 and Treg/Th17 ratios in patients with AD. AESS increased autophagy, improved skin barrier function, and inhibited Hippo-YAP signalling pathway activity. YAP knockdown reduces these therapeutic effects. Besides regulating immune imbalance, AESS increases keratinocyte autophagy levels, thereby restoring skin barrier function in AD through the Hippo-YAP signalling pathway. Trial Registration: The Chinese clinical trial registration website: ITMCTR202500042
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高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Peng Zhang,Luhao Liu,Weiting Zhang,Jiali Fang,Guanghui Li,Lei Zhang,Jiali Li,Xuanying Deng,Junjie Ma,Kun Li,Zheng Chen
To explore the function and mechanism of lncRNA HOXA-AS2 in cancer-associated fibroblasts (CAFs)-derived exosomes in gallbladder cancer metastasis, and provide new research targets for the treatment of gallbladder cancer. At the same time, in order to clarify the early predictive value of lncRNA HOXA-AS2 for gallbladder cancer metastasis, and to provide a theoretical basis for clinical individualized treatment of gallbladder cancer. Methods. In our previous work, we used TCGA database analysis to find that lncRNA HOXA-AS2 was highly expressed in gallbladder cancer tissues compared with normal tissues. In this study, the expression levels of HOXA-AS2 in gallbladder cancer cell lines and control cells were first verified by QPCR and Western blot methods. Then, lentiviral tools were used to construct knockdown vectors (RNAi#1, RNAi#2) and negative control vectors targeting two different sites of HOXA-AS2, and the vectors were transfected into NOZ and OCUG-1 cells, respectively. Real-time PCR was used to detect knockdown efficiency. Then, the effects of silencing HOXA-AS2 on the proliferation, cell viability, cell migration, and invasion ability of gallbladder cancer cells were detected by MTT, plate cloning assay, Transwell migration chamber assay, and Transwell invasion chamber assay. Finally, the interaction between HOXA-AS2 and miR-6867 and the 3UTR of YAP1 protein was detected by luciferase reporter gene. The results showed that the expression level of HOXA-AS2 in gallbladder cancer cell lines was higher than that in control cells. The expression of HOXA-AS2 in gallbladder carcinoma tissues was significantly higher than that in adjacent tissues (). After successful knockout of HOXA-AS2 by lentiviral transfection, the expression of HOXA-AS2 in gallbladder cancer cell lines was significantly decreased. Through cell proliferation and plate clone detection, it was found that silencing HOXA-AS2 inhibited cell proliferation and invasion. Through software prediction and fluorescein reporter gene detection, it was found that HOXA-AS2 has a binding site with miR-6867, and the two are negatively correlated, that is, the expression of miR-6867 is enhanced after the expression of HOXA-AS2 is downregulated. And the 3UTR of YAP1 protein in the Hippo signaling pathway binds to miR-6867. Therefore, HOXA-AS2 may affect the expression of YAP1 protein by regulating miR-6867, thereby inhibiting the Hippo signaling pathway and promoting the proliferation and metastasis of gallbladder cancer cells. HOXA-AS2 is abnormally expressed in gallbladder cancer cells. HOXA-AS2 may promote the migration and invasion of gallbladder cancer cells by regulating the Hippo signaling pathway through miR-6867. HOXA-AS2 may serve as a potential diagnostic and therapeutic target for gallbladder cancer in clinic.
研究领域:
分子生物学
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肿瘤学
·
细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 17
·e70815
·
IF 4.2
Yang Tian,Wei Li,Qing Zhai,Ying Yu,Jiaxin Yuan,Yan Ma,Jingjing Yang,Mingyue Li,Wenwen Chang,Wenjing Li,Keke Huang,Chongran Sun,Chen Zeng,Yingdi Sun,Jiabao Gu,Huilin Zhang,Dameng Li,Yanan Yu,Lu Hu,Peng Zhang,Bo Ma,Junnian Zheng,Pan Li,Feng Guo,Yang Sun
Protein S‐palmitoylation, a dynamic and reversible post‐translational modification involving the attachment of palmitate to cysteine residues, is a key regulator of protein functionality and cellular signalling. Dysregulation of this modification has emerged as a critical driver of cancer progression. Among the 23 DHHC palmitoyl transferases responsible for catalysing S‐palmitoylation, aberrant expression of specific members is linked to tumorigenesis and development, underscoring their potential as promising therapeutic targets. However, the cancer‐specific roles and substrates of individual DHHC enzymes remain poorly characterised. In this study, we identified DHHC9 as a crucial regulator of adenocarcinoma progression, including colorectal and lung cancers. Functional studies demonstrated that DHHC9 knockdown profoundly inhibited cell migration in vitro and tumour metastasis in vivo. Proteomic and functional analyses revealed that STRN4, a core component of the STRIPAK complex, was palmitoylated by DHHC9 at cysteine 701. The STRN4 palmitoylation reduced YAP phosphorylation, promoted nuclear translocation of YAP and activated downstream Hippo pathway transcriptional targets—including CCN1, CCN2 and ANKRD1—thereby driving cancer cell migration. Notably, we discovered two small molecules, Treprostinil and 10‐HCPT, as potent DHHC9 inhibitors that effectively suppressed adenocarcinoma cell migration. Our findings define the DHHC9‐STRN4‐YAP axis as a novel mechanism linking palmitoylation to phosphatase regulation and Hippo pathway dysregulation, unveiling DHHC9 as a highly promising therapeutic target in cancer treatment.
研究领域:
癌症生物学
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生物化学
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分子生物学
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药理学
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细胞信号传导
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）