MACC1 promotes pancreatic cancer metastasis by interacting with the EMT regulator SNAI1 DOI Creative Commons

Xianglian Zhang,

Ya Luo,

Yu Cen

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(11)

Published: Nov. 4, 2022

Metastasis is the dominant cause of cancer-related mortality. Metastasis-associated with colon cancer protein 1 (MACC1) has been proven to play a critical role in metastasis. However, prometastatic MACC1 regulating pancreatic (PC) metastatic phenotype remains elusive. Here, we report that highly expressed The Cancer Genome Atlas (TCGA) and tissue microarray (TMA) identified as good indicator for poor prognosis. Overexpression or knockdown PC cells correspondingly promoted inhibited cell migration invasion MET proto-oncogene receptor tyrosine kinase (MET)-independent manner. Notably, markedly decreased liver lesions metastasis model. Mechanistically, binds epithelial-mesenchymal transition (EMT) regulator snail family transcriptional repressor (SNAI1) drive EMT via upregulating activity SNAI1, leading transactivation fibronectin (FN1) trans-repression cadherin (CDH1). Collectively, our results unveil new mechanism by which drives suggest MACC1-SNAI1 complex-mediated mesenchymal may be therapeutic target cancer.

Language: Английский

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial DOI Creative Commons
Zev A. Wainberg, Davide Melisi, Teresa Macarulla

et al.

The Lancet, Journal Year: 2023, Volume and Issue: 402(10409), P. 1272 - 1281

Published: Sept. 11, 2023

Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, with few treatment options. NAPOLI 3 aimed to compare efficacy and safety NALIRIFOX versus nab-paclitaxel gemcitabine as first-line therapy for metastatic pancreatic (mPDAC).

Language: Английский

Citations

210
A review of Glycogen Synthase Kinase-3 (GSK3) inhibitors for cancers therapies DOI
Riya Thapa, Gaurav Gupta, Asif Ahmad Bhat

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 127375 - 127375

Published: Oct. 13, 2023

Language: Английский

Citations

89
Nomogram Predicts Risk and Prognostic Factors for Bone Metastasis of Pancreatic Cancer: A Population-Based Analysis DOI Creative Commons
Wei Zhang,

Lichen Ji,

Xijun Wang

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 12

Published: March 9, 2022

The overall survival (OS) of pancreatic cancer (PC) patients with bone metastasis (BM) is extremely low, and it pretty hard to treat metastasis. However, there are currently no effective nomograms predict the diagnosis prognosis (PCBM). Therefore, great significance establish predictive models guide clinical practice.We screened from Surveillance Epidemiology End Results (SEER) database between 2010 2016. independent risk factors PCBM were identified univariable multivariable logistic regression analyses, univariate multivariate Cox proportional hazards analyses used determine prognostic affecting PCBM. In addition, two constructed We area under curve (AUC), C-index calibration accuracy discriminability nomograms. decision analysis (DCA) Kaplan-Meier(K-M) curves employed further confirm effectiveness nomogram.Multivariable revealed that included age, primary site, histological subtype, N stage, radiotherapy, surgery, brain metastasis, lung liver Using we found race, grade, chemotherapy, utilized visually express data results. training cohort was 0.795 (95%CI: 0.758-0.832), whereas internal validation 0.800 0.739-0.862), external 0.787 0.746-0.828). Based on AUC receiver operating characteristic (ROC) analysis, plots, (DCA), concluded model exhibits excellent performance.Nomogram sufficiently accurate PCBM, allowing for individualized decisions future work.

Language: Английский

Citations

84
Preclinical Development of Magnetic Nanoparticles for Hyperthermia Treatment of Pancreatic Cancer DOI
Zamira V. Díaz‐Riascos, Monserrat Llaguno‐Munive, Nuria Lafuente-Gómez

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: 17(2), P. 2924 - 2939

Published: Jan. 2, 2025

Pancreatic ductal adenocarcinoma (PDAC) is a very challenging disease with poor prognosis. It characterized by dense desmoplastic stroma that hampers drug penetration and limits the effectiveness of conventional chemotherapy (CT). As an alternative, combination CT hyperthermia (HT) has been proposed as innovative treatment modality for PDAC. In previous works, we reported on development iron oxide magnetic nanoparticles (MNPs) that, when exposed to time-varying fields, exhibit strong HT responses inhibited growth pancreatic cancers. We report here advances toward clinical use these MNPs intratumorally administered sterile fluid (the "NoCanTher ThermoTherapy" or "NTT" Agent) alongside intravenous standard-of-care drugs (gemcitabine nab-paclitaxel) vitro cell viability assays show low doses highly synergistic, particularly in BxPC-3 line. vivo, biodistribution showed NTT Agent remained mainly within tumor, concentrated around areas high stromal component. Moreover, combined CT/HT shows clear advantages over alone terms reduction tumor volume, suggesting potential direct effect disruption interstitial facilitate access malignant cells. These studies have led approval commencement investigational study at Vall d'Hebron University Hospital (Barcelona, Spain) patients locally advanced

Language: Английский

Citations

2
Comprehensive machine-learning survival framework develops a consensus model in large-scale multicenter cohorts for pancreatic cancer DOI Creative Commons
Libo Wang, Zaoqu Liu,

Ruopeng Liang

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Oct. 25, 2022

As the most aggressive tumor, outcome of pancreatic cancer (PACA) has not improved observably over last decade. Anatomy-based TNM staging does exactly identify treatment-sensitive patients, and an ideal biomarker is urgently needed for precision medicine. Based on expression files 1280 patients from 10 multicenter cohorts, we screened 32 consensus prognostic genes. Ten machine-learning algorithms were transformed into 76 combinations, which selected optimal algorithm to construct artificial intelligence-derived signature (AIDPS) according average C-index in nine testing cohorts. The results training cohort, Meta-Cohort, three external validation cohorts (290 patients) consistently indicated that AIDPS could accurately predict prognosis PACA. After incorporating several vital clinicopathological features 86 published signatures, exhibited robust dramatically superior predictive capability. Moreover, other prevalent digestive system tumors, nine-gene still stratify prognosis. Of note, our had important clinical implications PACA, with low owned a dismal prognosis, higher genomic alterations, denser immune cell infiltrates as well more sensitive immunotherapy. Meanwhile, high group possessed prolonged survival, panobinostat may be potential agent AIDPS. Overall, study provides attractive tool further guide management individualized treatment

Language: Английский

Citations

61
Molecular and metabolic regulation of immunosuppression in metastatic pancreatic ductal adenocarcinoma DOI Creative Commons
Shailendra K. Gautam, Surinder K. Batra, Maneesh Jain

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: July 24, 2023

Immunosuppression is a hallmark of pancreatic ductal adenocarcinoma (PDAC), contributing to early metastasis and poor patient survival. Compared the localized tumors, current standard-of-care therapies have failed improve survival patients with metastatic PDAC, that necessecitates exploration novel therapeutic approaches. While immunotherapies such as immune checkpoint blockade (ICB) vaccines emerged promising treatment modalities in certain cancers, limited responses been achieved PDAC. Therefore, specific mechanisms regulating response immunotherapy must be explored. The immunosuppressive microenvironment driven by oncogenic mutations, tumor secretome, non-coding RNAs, microbiome persists throughout PDAC progression, allowing neoplastic cells grow locally metastasize distantly. escaping host surveillance are unique molecular, immunological, metabolic characteristics. Following chemokine exosomal guidance, these organ-specific pre-metastatic niches (PMNs) constituted local resident cells, stromal fibroblasts, suppressive metastasis-associated macrophages, neutrophils, myeloid-derived suppressor cells. differs from primary tumors cell composition, functionality, metabolism. Thus far, multiple molecular pathways, distinct identified dampen effector functions, confounding This review describes major immunoregulatory pathways contribute progression limit outcomes Overall, we highlight vulnerabilities attributable factors discuss whether targeting immunological "hot spots" could immunotherapies.

Language: Английский

Citations

41
Gemcitabine effects on tumor microenvironment of pancreatic ductal adenocarcinoma: Special focus on resistance mechanisms and metronomic therapies DOI Open Access
Jay Z. Natu, Ganji Purnachandra Nagaraju

Cancer Letters, Journal Year: 2023, Volume and Issue: 573, P. 216382 - 216382

Published: Sept. 2, 2023

Language: Английский

Citations

37
Chemotherapeutic drugs-induced pyroptosis mediated by gasdermin E promotes the progression and chemoresistance of pancreatic cancer DOI
Shumin Li, Yue Ming, Haiyan Xu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 564, P. 216206 - 216206

Published: April 28, 2023

Language: Английский

Citations

36
hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma DOI Creative Commons

Lei Xu,

Xiao Ma, Xiuzhong Zhang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Dec. 3, 2023

Abstract Background Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer chemoresistance. DNA damage repair contributes to proliferation cells resistance chemotherapy-induced apoptosis. However, role circRNAs regulation needs clarification. Methods RNA sequencing analysis was applied identify differentially expressed circRNAs. qRT-PCR conducted confirm expression hsa_circ_0007919, CCK-8, FCM, single-cell gel electrophoresis IF assays were used analyze proliferation, apoptosis gemcitabine (GEM) pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model IHC experiments effects hsa_circ_0007919 on tumor growth vivo. GSEA downstream genes pathways hsa_circ_0007919. FISH nuclear-cytoplasmic fractionation cellular localization ChIRP, RIP, Co-IP, ChIP, MS-PCR luciferase reporter interaction among FOXA1, TET1 LIG1 promoter. Results We identified a highly circRNA, GEM-resistant PDAC tissues High correlates with poor overall survival (OS) disease-free (DFS) patients. Hsa_circ_0007919 inhibits damage, accumulation breaks induced by GEM LIG1-dependent manner maintain cell survival. Mechanistically, recruits FOXA1 decrease methylation promoter increase its transcription, further promoting base excision repair, mismatch nucleotide repair. At last, we found that enhanced binding QKI introns pre-mRNA splicing circularization this generate Conclusions promotes enhancing Targeting could be therapeutic strategy for PDAC.

Language: Английский

Citations

25
Extracellular vesicle-mediated pre-metastatic niche formation via altering host microenvironments DOI Creative Commons
Ying Li, Yan Zheng,

Xiaojie Tan

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 1, 2024

The disordered growth, invasion and metastasis of cancer are mainly attributed to bidirectional cell-cell interactions. Extracellular vesicles (EVs) secreted by cells involved in orchestrating the formation pre-metastatic niches (PMNs). Tumor-derived EVs mediate communication between tumor stromal local distant microenvironments. carrying mRNAs, small RNAs, microRNAs, DNA fragments, proteins metabolites determine metastatic organotropism, enhance angiogenesis, modulate stroma cell phenotypes, restructure extracellular matrix, induce immunosuppression modify metabolic environment organs. Evidence indicates that educate secondary sites establish metastasis-supportive microenvironments for seeding cells. In this review, we provide a comprehensive overview PMN underlying mechanisms mediated EVs. Potential approaches inhibit inhibiting PMNs also presented.

Language: Английский

Citations

15