Calpain 8 as a potential biomarker regulates the progression of pancreatic cancer via EMT and AKT/ERK pathway

Song, Na; Cui, Kai; Zeng, Liqun; Fan, Yanwu; Wang, Ziwei; Shi, Pingyu; Su, Wei; Wang, Haijun

doi:10.1016/j.jprot.2024.105182

Cited by 6 publications

References 56 publications

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Genetic requirement ofdact1/2to regulate noncanonical Wnt signaling andcalpain 8during embryonic convergent extension and craniofacial morphogenesis

Carroll,

Schafer,

Kawasaki

et al. 2023

Preprint

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Wnt signaling plays a crucial role in the early embryonic patterning and development, to regulate convergent extension during gastrulation and the establishment of the dorsal axis. Further, Wnt signaling is a crucial regulator of craniofacial morphogenesis. The adapter proteins Dact1 and Dact2 modulate the Wnt signaling pathway through binding to Disheveled, however, the distinct relative functions of Dact1 and Dact2 during embryogenesis remain unclear. We found thatdact1anddact2genes have dynamic spatiotemporal expression domains that are reciprocal to one another and townt11f2l, that suggest distinct functions during zebrafish embryogenesis. We found that bothdact1anddact2contribute to axis extension, with compound mutants exhibiting a similar convergent extension defect and craniofacial phenotype to thewnt11f2mutant. Utilizing single-cell RNAseq andgpc4mutant that disrupts noncanonical Wnt signaling, we identifieddact1/2specific roles during early development. Comparative whole transcriptome analysis between wildtype,gpc4anddact1/2mutants revealed a novel role fordact1/2in regulating the mRNA expression of the classical calpaincapn8. Over-expression ofcapn8phenocopiesdact1/2craniofacial dysmorphology. These results identify a previously unappreciated role ofcapn8and calcium-dependent proteolysis during embryogenesis. Taken together, our findings highlight the distinct and overlapping roles ofdact1anddact2in embryonic craniofacial development, providing new insights into the multifaceted regulation of Wnt signaling.

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Genetic requirement ofdact1/2to regulate noncanonical Wnt signaling andcalpain 8during embryonic convergent extension and craniofacial morphogenesis

Carroll,

Schafer,

Kawasaki

et al. 2023

Preprint

View full text Add to dashboard Cite

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A Comparison of Tools That Identify Tumor Cells by Inferring Copy Number Variations from Single-Cell Experiments in Pancreatic Ductal Adenocarcinoma

Oketch,

Giulietti,

Piva

2024

Biomedicines

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Single-cell RNA sequencing (scRNA-seq) technique has enabled detailed analysis of gene expression at the single cell level, enhancing the understanding of subtle mechanisms that underly pathologies and drug resistance. To derive such biological meaning from sequencing data in oncology, some critical processing must be performed, including identification of the tumor cells by markers and algorithms that infer copy number variations (CNVs). We compared the performance of sciCNV, InferCNV, CopyKAT and SCEVAN tools that identify tumor cells by inferring CNVs from scRNA-seq data. Sequencing data from Pancreatic Ductal Adenocarcinoma (PDAC) patients, adjacent and healthy tissues were analyzed, and the predicted tumor cells were compared to those identified by well-assessed PDAC markers. Results from InferCNV, CopyKAT and SCEVAN overlapped by less than 30% with InferCNV showing the highest sensitivity (0.72) and SCEVAN the highest specificity (0.75). We show that the predictions are highly dependent on the sample and the software used, and that they return so many false positives hence are of little use in verifying or filtering predictions made via tumor biomarkers. We highlight how critical this processing can be, warn against the blind use of these software and point out the great need for more reliable algorithms.

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Genetic requirement of dact1/2 to regulate noncanonical Wnt signaling and calpain 8 during embryonic convergent extension and craniofacial morphogenesis

Carroll,

Schafer,

Kawasaki

et al. 2024

eLife

View full text Add to dashboard Cite

Wnt signaling plays a crucial role in the early embryonic patterning and development, to regulate convergent extension during gastrulation and the establishment of the dorsal axis. Further, Wnt signaling is a crucial regulator of craniofacial morphogenesis. The adapter proteins Dact1 and Dact2 modulate the Wnt signaling pathway through binding to Disheveled, however, the distinct relative functions of Dact1 and Dact2 during embryogenesis remain unclear. We found that dact1 and dact2 genes have dynamic spatiotemporal expression domains that are reciprocal to one another and to wnt11f2l , that suggest distinct functions during zebrafish embryogenesis. We found that both dact1 and dact2 contribute to axis extension, with compound mutants exhibiting a similar convergent extension defect and craniofacial phenotype to the wnt11f2 mutant. Utilizing single-cell RNAseq and gpc4 mutant that disrupts noncanonical Wnt signaling, we identified dact1/2 specific roles during early development. Comparative whole transcriptome analysis between wildtype, gpc4 and dact1/2 mutants revealed a novel role for dact1/2 in regulating the mRNA expression of the classical calpain capn8 . Over-expression of capn8 phenocopies dact1/2 craniofacial dysmorphology. These results identify a previously unappreciated role of capn8 and calcium-dependent proteolysis during embryogenesis. Taken together, our findings highlight the distinct and overlapping roles of dact1 and dact2 in embryonic craniofacial development, providing new insights into the multifaceted regulation of Wnt signaling.

show abstract

Calpain 8 as a potential biomarker regulates the progression of pancreatic cancer via EMT and AKT/ERK pathway

Cited by 6 publications

References 56 publications

Genetic requirement ofdact1/2to regulate noncanonical Wnt signaling andcalpain 8during embryonic convergent extension and craniofacial morphogenesis

Genetic requirement ofdact1/2to regulate noncanonical Wnt signaling andcalpain 8during embryonic convergent extension and craniofacial morphogenesis

A Comparison of Tools That Identify Tumor Cells by Inferring Copy Number Variations from Single-Cell Experiments in Pancreatic Ductal Adenocarcinoma

Genetic requirement of dact1/2 to regulate noncanonical Wnt signaling and calpain 8 during embryonic convergent extension and craniofacial morphogenesis

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