USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer DOI Creative Commons

Pan Chi,

Zhongdong Xie,

Hanbin Lin

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 21, 2024

Abstract Metastasis is a major challenge for colorectal cancer (CRC) treatment. Here, we uncovered CENPF may be involved in CRC metastasis through bioinformatics mining and small interfering RNA (siRNA) targeted functional screening. We observed expression was preferentially increased tissues compared to adjacent normal tissues. More importantly, multicenter cohort study identified upregulated significantly correlated with poor survival CRC. Knockdown of inhibited cell invasion vitro vivo. Intriguingly, found undergoes degradation via the ubiquitination-proteasome pathway. Mechanistically, that USP4 interacted stabilized deubiquitination. Furthermore, USP4-mediated upregulation critical regulators Examination clinical samples confirmed positively correlates protein expression, but not mRNA transcript levels. Taken together, this describes novel USP4-CENPF signaling axis which crucial metastasis, potentially serving as therapeutic target promising prognostic biomarker

Язык: Английский

Single-cell and spatial transcriptome profiling reveal CTHRC1+ fibroblasts promote EMT through WNT5A signaling in colorectal cancer DOI Creative Commons
Yunfei Lu, Yang Chen, Zhenling Wang

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 6, 2025

Cancer-associated fibroblasts (CAFs), known for facilitating the progression and metastasis of colorectal cancer (CRC), have become a promising therapeutic target. However, significant heterogeneity CAFs their intricate crosstalk with tumor cells present substantial challenges in development precise effective strategies. Single-cell RNA sequencing (scRNA-seq) technology was used to identify various cell subtypes. Spatial transcriptomics (ST) employed map spatial niches colocalization patterns these Cell-cell interactions among subtypes were analysed via CellChat NicheNet software. Tumor invasion, migration, proliferation assessed through wound healing assays, transwell colony formation xenograft mouse models. We identified between CTHRC1+ distinct subtype malignant epithelial cells, both residing within EMT-active niche. Our results demonstrate that CAFs, as major source WNT5A, promote epithelial-mesenchymal transition (EMT) enhance invasiveness by upregulating MSLN expression adjacent cells. This signaling axis contributes significantly CRC metastasis. Targeting CAF-WNT5A-MSLN presents strategy advanced patients. study provides new insights into role offers potential avenues developing targeted therapies disrupt this pathway.

Язык: Английский

Процитировано

2
USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer DOI Creative Commons

Zhongdong Xie,

Hanbin Lin,

Yuecheng Wu

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 8, 2025

Язык: Английский

Процитировано

0
Bisphenol S Promotes Clear Cell Renal Cell Carcinoma Progression by Modulating the WNT5A-Dependent EMT Pathway DOI
Hua Zhang, Fei Lin,

Bo-Han Lin

и другие.

Toxicology, Год журнала: 2025, Номер unknown, С. 154117 - 154117

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Gestational high-sucrose diet mediated vascular hyper-contractility in mesenteric arteries from offspring DOI Creative Commons
Xinying Liu, Meng Liu,

Chunxia Wang

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 17, 2025

Prenatal high sucrose diet (HS) generates profound effects on vascular diseases in offspring later life. This study aimed to determine whether and how prenatal HS affect vasoreactivity resistance arteries from adult offspring. Pregnant Sprague-Dawley rats were fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Mesenteric (MAs) obtained tested for functions DMT. The whole-transcriptome sequencing (RNA-seq) of MAs was performed reveal different genes possible pathway. Real-time PCR western blot access mRNA protein expression. thicker smooth muscle layer mitochondrial swelling observed mediated higher vasoconstriction/vascular sensitivity induced by phenylephrine (PE) 5-Hydroxytryptamine (5-HT). RNA-Seq analysis revealed that crystallin alpha B (CYRAB) heat shock family E member 1 (HSPE1) upregulated, while gene adenomatous polyposis coli downregulated (APCDD1) group, confirmed at expression levels. Wingless-related integration site (Wnt)/Ca2+ indicated KEGG essential pathway inducing dysfunction group. As a Wnt5a inhibitor, Box5 reduced MA tension PE 5-HT Both kinase C (PKC) inhibitor-GF109203X Inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor-2-Aminoethoxydiphenyl borate (2-APB) significantly decreased tone Ca2+ levels markedly than control (CON), likely contributing enhanced reactivity. Vascular relaxation acetylcholine (ACh) lower CON. N(G)-Nitro-l-arginine methyl ester (L-NAME) increased PE-mediated CON no effect suggesting endothelial nitric oxide (NO) system exposed HS. demonstrated hyper-vasocontraction offspring, which associated Wnt5a-PKC/IP3R-Ca2+ NO function.

Язык: Английский

Процитировано

0
Inhibition of stromal MAOA leading activation of WNT5A enhance prostate cancer immunotherapy by involving the transition of cancer-associated fibroblasts DOI Creative Commons

Zhite Zhao,

Yaohua Hu,

Hui Li

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(3), С. e010555 - e010555

Опубликована: Март 1, 2025

Background The interaction between stromal cells and the tumor immune microenvironment (TIME) is acknowledged as a critical driver in progression of prostate cancer (PCa). Monoamine oxidase A (MAOA), mitochondrial enzyme that catalyzes degradation monoamine neurotransmitters dietary amines, has been linked to promotion tumorigenesis, particularly when upregulated cells. However, detailed mechanisms MAOA’s with TIME have not fully elucidated. Methods We reanalyzed single-cell sequencing dataset evaluate role MAOA stroma, verify impact alterations on CD8 + T cell responses by co-culturing vitro. Furthermore, C57BL/6J mouse subcutaneous transplant models dual humanized were established investigate function vivo potential its inhibitors for immunotherapy. Results Our study demonstrates inhibiting facilitates conversion myofibroblastic cancer-associated fibroblasts (myCAFs), thereby improving immunosuppressive environment PCa. strategic combination inhibition checkpoint elicits synergistic antitumor effect. Specifically, leads increased production WNT5A, which subsequently activates cytotoxic capacity through Ca 2+ -NFATC1 signaling pathway. Conclusions findings highlight modulating within PCa microenvironment, presenting novel therapeutic strategy augment efficacy immunotherapy

Язык: Английский

Процитировано

0
Recent advances in understanding the role of Wnt5a in prostate cancer and bone metastasis DOI Creative Commons
Qiuping Xie,

Guang‐Quan Zhao,

Hao Tang

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Май 23, 2025

Язык: Английский

Процитировано

0
Therapeutic Potential of Targeting PCLAF in Endometrial Cancer: Insights from Wnt/β-catenin and p53 Regulatory Mechanisms DOI Creative Commons
Wenhua Wang, Yijuan Xing, Xi Chen

и другие.

Biochemical and Biophysical Research Communications, Год журнала: 2025, Номер 774, С. 152092 - 152092

Опубликована: Май 26, 2025

Endometrial cancer (EC), a widespread gynecological malignancy, has limited therapeutic options, particularly in patients with advanced, metastatic, or recurrent disease. PCLAF, proliferation-related protein, is overexpressed several tumors; however, its role and mechanism EC remain largely unknown. Ten hub genes were identified predicted through bioinformatics analyses. The expression of PCLAF was validated using molecular biology technology, while function investigated vitro proliferation, cell cycle, migration, apoptosis assays. Mechanistically, the transcriptome proteome sequencing revealed potential regulatory pathways for EC. Finally, experiments on animals executed to test Ishikawa growth vivo. exhibited high both cells tissues. Silencing significantly impaired migration invasion, blocked G1 phase progression cycle activated apoptosis. Sequencing results western blot analysis confirmed that knockdown inhibits Wnt/β-catenin pathway activates p53 pathway. vivo effectively inhibited growth. In conclusion, our findings suggest silencing hinders by suppressing activating signaling This insight suggested targeting may offer new avenue treatment.

Язык: Английский

Процитировано

0
The Interplay among Wnt/β-Catenin Family Members in Colorectal Adenomas and Surrounding Tissues DOI Open Access

Domenica Lucia D’Antonio,

Fabiana Fantini,

Carmelo Moscatello

и другие.

Опубликована: Июнь 24, 2024

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in Vogelgram. The risk of developing cancer is strongly associated with number and size subtype. Currently, adenomatous polyps can be distinguished on basis histology: prevalence are tubular, 5-15% villous tubular/villous. Considering increased for malignant transformation described tubular/villous adenomas, patients diagnosed polyposis at CRC. Wnt/β-catenin pathway plays a key role onset colorectal adenoma, particular intestinal cells first acquire loss-of-function mutations APC gene that induce formation adenomas. Methods: APC, Wnt3a, Wnt5a, LEF1, BCL9 genes protein expression analyses were conducted by qRT-PCR western blot 68 colonic samples (polyps adjacent mucosa) from 41 patients, which 17 affected FAP. Ten mucosal collected 10 healthy donors. Results: In this study both resulted less expressed colon tumor compared to mucosa. Conversely, activated β-catenin was more than All results confirmed literature data carcinomas. A statistically significant correlation between Wnt3a mucosa underlies canonical Wnt early carcinogenesis already altered. Conclusion: This analyzing difference human Understanding adenomas carcinomas essential development new therapeutic strategies improving clinical outcomes.

Язык: Английский

Процитировано

2
Identification of BGN positive fibroblasts as a driving factor for colorectal cancer and development of its related prognostic model combined with machine learning DOI Creative Commons
Shangshang Hu,

Qianni Xiao,

Rui Gao

и другие.

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Апрель 23, 2024

Numerous studies have indicated that cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, there are still many unknowns regarding exact CAF subtypes CRC.

Язык: Английский

Процитировано

1
Wnt5a promotes VM formation by modulating the stemness and EMT progression of prostate cancer cell DOI Creative Commons

Bide Liu,

Xun Li, Shuheng Wang

и другие.

Translational Oncology, Год журнала: 2024, Номер 51, С. 102155 - 102155

Опубликована: Ноя. 1, 2024

Язык: Английский

Процитировано

1