Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk

Zhao, Lingling; Liu, Hongliang; Luo, Sheng; Moorman, Patricia G.; Walsh, Kyle M.; Li, Wei; Wei, Qingyi

doi:10.1002/cam4.3603

Cited by 3 publications

(3 citation statements)

References 61 publications

(107 reference statements)

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“…Not only have formin levels been associated with cancer prognosis, but gene variants and deletions have also been associated with the risk of cancer progression. For example, specific FMN1 variants have been linked to a higher risk of developing pancreatic [300] and prostate cancer [304]. In lung cancer, a variant in the FH2 domain of DAAM2 (p.Asp762Gly) has been associated with a protective effect, and, although not a statistically significant result, a variant in the DID (p.Arg172His) was found to be enriched in healthy controls [292].…”

Section: Formins As Prognostic Biomarkers and Therapeutical Targets In Cancermentioning

confidence: 99%

Formins in Human Disease

Labat-de-Hoz

Alonso

2021

Cells

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Almost 25 years have passed since a mutation of a formin gene, DIAPH1, was identified as being responsible for a human inherited disorder: a form of sensorineural hearing loss. Since then, our knowledge of the links between formins and disease has deepened considerably. Mutations of DIAPH1 and six other formin genes (DAAM2, DIAPH2, DIAPH3, FMN2, INF2 and FHOD3) have been identified as the genetic cause of a variety of inherited human disorders, including intellectual disability, renal disease, peripheral neuropathy, thrombocytopenia, primary ovarian insufficiency, hearing loss and cardiomyopathy. In addition, alterations in formin genes have been associated with a variety of pathological conditions, including developmental defects affecting the heart, nervous system and kidney, aging-related diseases, and cancer. This review summarizes the most recent discoveries about the involvement of formin alterations in monogenic disorders and other human pathological conditions, especially cancer, with which they have been associated. In vitro results and experiments in modified animal models are discussed. Finally, we outline the directions for future research in this field.

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Section: Formins As Prognostic Biomarkers and Therapeutical Targets In Cancermentioning

confidence: 99%

Formins in Human Disease

Labat-de-Hoz

Alonso

2021

Cells

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“…It was imperative to investigate if the EVs that were injected into the mice could in uence any biological activity. Several studies [67][68][69][70] have shown that there is a distinct pancreatic microbiome which could decisively in uence the development of pancreatic cancer. To investigate this phenomenon, fecal pellets were collected from mice who were injected with PBS control or with EVs from KPC, PSC and co-culture conditions two weeks after education.…”

Section: Discussionmentioning

confidence: 99%

Rapid and Multifaceted Characterization of the Effects of the Secreted EVome in Pancreatic Cancer: A Global Omics Approach for Screening Putative Biomarkers

Jacob

Signorelli

Richard

et al. 2022

Preprint

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Background: Pancreatic cancer is one of the most difficult cancers to detect early and most patients die from complications arising due to distant organ metastases. The lack of bona fide biomarkers is one of the primary reasons for the late diagnosis of this cancer. Most researchers have focused on screening strategies to characterize biomarkers that show promise in preclinical models but eventually fail in a clinical scenario. Pancreatic cancer is a multifactorial disease and warrants a multi-omics approach to identify novel biomarkers for early diagnosis. Methods: In order to characterize the proteome, Extracellular vesicles (EVs) isolated from different in vitro conditions mimicking interactions between pancreatic cancer epithelial and stromal cells were isolated and subjected to high throughput mass spectrometry. Biological activity of the secreted EVome was analyzed by investigating changes in distant organ metastases and early changes in the microbiome. Putative biomarkers were selected and validated using a mouse-human hybrid TMA that was specifically generated for this study. As potential targets, immunohistochemical analysis of protein candidates (Kif5b, Sfpr2, Loxl2, and Mmp3) was performed on the TMA to assess their potential as candidates for early discovery of pancreatic cancer. Results: The EVome of epithelial and stromal cells co-cultured with each other is distinctly different from individual cells with distinct protein compositions. While these proteomes could not induce significant changes in Pre-Metastatic Niche (PMN) modulation and distant organ metastases, they did induce significant early changes in the microbiome, as indicated by changes in the α and β-diversities in experimental animal models. Novel biomarkers validated in this study, such as Kif5b and Sfrp2 show promise for early detection and investigation of pancreatic cancer. Conclusions: Multi-omics analyses of EVs from mimicking conditions of tumor stromal interactions resulted in the identification of Kif5b and Sfrp2 as bona fide biomarkers with biological activity which could prove to be immensely helpful in improving early detection and diagnosis of pancreatic cancer.

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“…Its mutation, regulating filamin expression and neuronal migration [ 7 ], was detected in breast neuroendocrine neoplasms (NENs), a peculiar histologic subtype [ 93 ]. Genome-wide sequencing shows that MAP3K4 and its mutations also frequently appear in several kinds of tumor tissues, such as serous endometrial tumor [ 94 ], wilms tumor [ 95 ], EBV-positive gastric tumor [ 96 ], pancreatic cancer [ 97 ], and family lung cancer [ 98 ].…”

Section: The Complex Function Of Map3k4 Concerning Tumormentioning

confidence: 99%

MAP3K4 kinase action and dual role in cancer

Huang,

Wang,

Zhang

et al. 2024

Discov Onc

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It is commonly known that the MAPK pathway is involved in translating environmental inputs, regulating downstream reactions, and maintaining the intrinsic dynamic balance. Numerous essential elements and regulatory processes are included in this pathway, which are essential to its functionality. Among these, MAP3K4, a member of the serine/threonine kinases family, plays vital roles throughout the organism's life cycle, including the regulation of apoptosis and autophagy. Moreover, MAP3K4 can interact with key partners like GADD45, which affects organism's growth and development. Notably, MAP3K4 functions as both a tumor promotor and suppressor, being activated by a variety of factors and triggering diverse downstream pathways that differently influence cancer progression. The aim of this study is to provide a brief overview of physiological functions of MAP3K4 and shed light on its contradictory roles in tumorigenesis.

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Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 3 publications

References 61 publications

Formins in Human Disease

Formins in Human Disease

Rapid and Multifaceted Characterization of the Effects of the Secreted EVome in Pancreatic Cancer: A Global Omics Approach for Screening Putative Biomarkers

MAP3K4 kinase action and dual role in cancer

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