CES2 sustains HNF4α expression to promote pancreatic adenocarcinoma progression through an epoxide hydrolase-dependent regulatory loop

Chen, Yihui; Capello, Michela; Perez, Mayrim V. Rios; Vykoukal, Jody; Roife, David; Kang, Ya’an; Prakash, Laura R.; Katayama, Hiroyuki; Irajizad, Ehsan; Fleury, Alia; Ferri-Borgogno, Sammy; Baluya, Dodge L.; Dennison, Jennifer B.; Do, Kim‐Anh; Fiehn, Oliver; Maitra, Anirban; Wang, Huamin; Chiao, Paul J.; Katz, Matthew H.; Fleming, Jason B.; Hanash, Samir M.; Fahrmann, Johannes F.

doi:10.1016/j.molmet.2021.101426

Cited by 15 publications

(21 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression levels of CES2 are heterogeneous in human cancers. Downregulation of CES2 expression has been found in cholangiocarcinoma [ 27 ], while CES2 upregulation has been found in pancreatic ductal adenocarcinoma (PDAC) [ 28 , 29 ] and neuroblastoma [ 30 ]. Over decades, CES2 has been found to be correlated with cancer patient clinical outcomes because it plays a role in activating the metabolism of anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma

Chen

Liu

Chen

et al. 2022

Molecular Metabolism

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma

Chen

Liu

Chen

et al. 2022

Molecular Metabolism

View full text Add to dashboard Cite

“…21,22 Recent studies have shown that CES2 plays an important role in the development of colorectal, neuroblastoma, and pancreatic cancers. [13][14][15] However, the molecular function of CES2 in BRCA has not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery

Qu¹,

Yao²,

Liu³

et al. 2023

IJGM

View full text Add to dashboard Cite

The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA. Patients and Methods: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays. Results: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models. Conclusion:CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.

show abstract

“…Total RNA extraction and qPCR was performed as previously described [13, 17]. Briefly, Total RNA was extracted using the RNeasy Mini Kit (Cat.…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA extraction and qPCR was performed as previously described [13,17] and subsequently transferred to PVDF membranes using the Trans-Blot Turbo system (BioRad).…”

Section: Total Rna Extraction and Quantitative Pcr (Qpcr)mentioning

confidence: 99%

EGFR inhibition in lung adenocarcinoma upregulates cell surface expression of the placental antigen ALPP and enhances efficacy of ALPP-ADC therapy

Chen

Hong

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Alkaline phosphatase placental type (ALPP) and ALPPL2 are closely related and regulated GPI anchored proteins that are known to be expressed on the cell surface in some cancers, whereas normal tissue expression is largely limited to the placenta. Clinical utility of ALPP is potentially limited by heterogenous expression in tumors. Here, we assessed ALPP and ALPPL2 surfaceome protein levels in 158 cancer cell lines and mRNA expression levels in 10,967 tumors representing 32 cancer types from The Cancer Genome Atlas (TCGA), which revealed ALPP, and to a lesser extent ALPPL2, to be variably expressed in several cancer types including lung adenocarcinoma (LUAD). Surface expression of ALPP was confirmed by tissue microarray analysis of 204 lung tumors. Using LUAD as a model system, we demonstrated that treatment with EGFR inhibitors, or induction of cancer cell quiescence via nutrient deprivation greatly enhanced ALPP surface expression. Mechanistic studies revealed that enhancement of surface ALPP expression in LUAD following gefitinib treatment was mediated through repression of EGFR signaling and activation of the transcription factor FoxO3a, which was identified as an upstream transcriptional regulator of ALPP. Using xenograft models of LUAD, we further demonstrated that gefitinib treatment upregulates surface expression of ALPP in LUAD cells but not in normal tissues. Combination therapy with gefitinib and an ALPP antibody conjugated with Monomethylauristatin F (ALPP-ADC-MAF) resulted in superior anti-cancer efficacy compared with gefitinib or ALPP-ADC-MAF alone. Our findings support a novel combination treatment modality that boosts the efficacy of ALPP-ADC directed therapy.

show abstract

CES2 sustains HNF4α expression to promote pancreatic adenocarcinoma progression through an epoxide hydrolase-dependent regulatory loop

Cited by 15 publications

References 47 publications

Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma

Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma

Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery

EGFR inhibition in lung adenocarcinoma upregulates cell surface expression of the placental antigen ALPP and enhances efficacy of ALPP-ADC therapy

Contact Info

Product

Resources

About