Altered chondrocyte differentiation, matrix mineralization and MEK-Erk1/2 signaling in an INPPL1 catalytic knock-out mouse model of opsismodysplasia

Catsyne, Charles Andrew Vande; Sayyed, Sufyan; Molina-Ortíz, Patricia; Moës, Bastien; Communi, David; Muller, Joséphine; Heusschen, Roy; Caers, Jo; Azzi, Abdelhalim; Erneux, Christophé; Schurmans, Stéphane

doi:10.1016/j.jbior.2019.100651

Cited by 7 publications

(9 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, it has been demonstrated that 5-phosphatases, such as Src homology 2-containing inositol 5-phosphatase (SHIP) in hematopoietic cells [8], Phosphatidylinositol 4,5-Bisphosphate 5-Phosphatase (PIB5PA) in neuritis and melanoma cells [9,10], and Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) in glioblastoma and GC cells, inhibit Akt activation [11,12]. SHIP2, encoded by inositol polyphosphate phosphatase-like 1 (INPPL1), belongs to the phosphoinositide 5-phosphatase family, which has been implicated in some human diseases such as type 2 diabetes, Alzheimer's disease and Opsismodysplasia [13][14][15]. However, the role of SHIP2 in tumorigenesis and tumor progression remains paradoxical: high SHIP2 expression has been found in breast cancer, hepatocellular cancer, non-small cell lung cancer, and colorectal cancer, which correlates with poor survival of patients and contributes to the malignant potential of these tumors [16][17][18][19], whereas reduced expression of SHIP2 in GC promotes tumorigenesis and proliferation of GC via activation of the PI3K/Akt signaling [12], and, in squamous cell carcinoma and glioblastoma cells, SHIP2 inhibits Akt activation and leads to apoptosis and cell cycle arrest [11,20].…”

mentioning

confidence: 99%

IQGAP2 Inhibits Migration and Invasion of Gastric Cancer Cells via Elevating SHIP2 Phosphatase Activity

Shao

Ren

et al. 2020

IJMS

View full text Add to dashboard Cite

Previous studies have shown reduced expression of Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) and its tumor-suppressive role in gastric cancer (GC). However, the precise role of SHIP2 in the migration and invasion of GC cells remains unclear. Here, an IQ motif containing the GTPase-activating protein 2 (IQGAP2) as a SHIP2 binding partner, was screened and identified by co-immunoprecipitation and mass spectrometry studies. While IQGAP2 ubiquitously expressed in GC cells, IQGAP2 and SHIP2 co-localized in the cytoplasm of GC cells, and this physical association was confirmed by the binding of IQGAP2 to PRD and SAM domains of SHIP2. The knockdown of either SHIP2 or IQGAP2 promoted cell migration and invasion by inhibiting SHIP2 phosphatase activity, activating Akt and subsequently increasing epithelial–mesenchymal transition (EMT). Furthermore, knockdown of IQGAP2 in SHIP2-overexpressing GC cells reversed the inhibition of cell migration and invasion by SHIP2 induction, which was associated with the suppression of elevated SHIP2 phosphatase activity. Moreover, the deletion of PRD and SAM domains of SHIP2 abrogated the interaction and restored cell migration and invasion. Collectively, these results indicate that IQGAP2 interacts with SHIP2, leading to the increment of SHIP2 phosphatase activity, and thereby inhibiting the migration and invasion of GC cells via the inactivation of Akt and reduction in EMT.

show abstract

mentioning

confidence: 99%

IQGAP2 Inhibits Migration and Invasion of Gastric Cancer Cells via Elevating SHIP2 Phosphatase Activity

Shao

Ren

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…MAPK3 was discovered as a particularly interesting candidate gene for outer ear development of lop eared pigs, known to play an essential role in the MAPK/ERK cascade, which mediates various biological processes such as cell growth, adhesion, survival and differentiation by regulating transcription, translation and rearrangements of the cytoskeleton [ 53 ]. Furthermore, MAPK was shown to be an important protagonist in chondrocyte differentiation and cartilage tissue formation processes [ 54 , 55 ]. It was found to be involved in a signalling cascade initiated by KIT (also located in lop-ear associated ROHR) and therefore might support the formation of ear cartilage tissue as well.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous testing of rule- and model-based approaches for runs of homozygosity detection opens up a window into genomic footprints of selection in pigs

et al. 2022

View full text Add to dashboard Cite

Background Past selection events left footprints in the genome of domestic animals, which can be traced back by stretches of homozygous genotypes, designated as runs of homozygosity (ROHs). The analysis of common ROH regions within groups or populations displaying potential signatures of selection requires high-quality SNP data as well as carefully adjusted ROH-defining parameters. In this study, we used a simultaneous testing of rule- and model-based approaches to perform strategic ROH calling in genomic data from different pig populations to detect genomic regions under selection for specific phenotypes. Results Our ROH analysis using a rule-based approach offered by PLINK, as well as a model-based approach run by RZooRoH demonstrated a high efficiency of both methods. It underlined the importance of providing a high-quality SNP set as input as well as adjusting parameters based on dataset and population for ROH calling. Particularly, ROHs ≤ 20 kb were called in a high frequency by both tools, but to some extent covered different gene sets in subsequent analysis of ROH regions common for investigated pig groups. Phenotype associated ROH analysis resulted in regions under potential selection characterizing heritage pig breeds, known to harbour a long-established breeding history. In particular, the selection focus on fitness-related traits was underlined by various ROHs harbouring disease resistance or tolerance-associated genes. Moreover, we identified potential selection signatures associated with ear morphology, which confirmed known candidate genes as well as uncovered a missense mutation in the ABCA6 gene potentially supporting ear cartilage formation. Conclusions The results of this study highlight the strengths and unique features of rule- and model-based approaches as well as demonstrate their potential for ROH analysis in animal populations. We provide a workflow for ROH detection, evaluating the major steps from filtering for high-quality SNP sets to intersecting ROH regions. Formula-based estimations defining ROHs for rule-based method show its limits, particularly for efficient detection of smaller ROHs. Moreover, we emphasize the role of ROH detection for the identification of potential footprints of selection in pigs, displaying their breed-specific characteristics or favourable phenotypes.

show abstract

“…The INPPL1 gene encodes SHIP2 protein that plays an important role in chondrocytes during endochondral ossification and differentiation. 19 Variants in INPLL1 gene have been reported to be the genetic cause in several cases of opsismodysplasia and one case of Schneckenbecken dysplasia (see Table 1). Presence of INPPL1 mutation-negative cases of opsismodysplasia and known molecular defects in SLC35D1 gene causing Schneckenbecken dysplasia should suggest genetic heterogeneity of both disorders.…”

Section: Discussionmentioning

confidence: 99%

“…The INPPL1 gene encodes SHIP2 protein that plays an important role in chondrocytes during endochondral ossification and differentiation 19 . Variants in INPLL1 gene have been reported to be the genetic cause in several cases of opsismodysplasia and one case of Schneckenbecken dysplasia (see Table 1).…”

Section: Discussionmentioning

confidence: 99%

Prenatal‐onset INPPL1‐related skeletal dysplasia in two unrelated families: Diagnosis and prediction of lethality

Abumansour

Iskandarani

Edrees

et al. 2021

Clinical Case Reports

View full text Add to dashboard Cite

This report describes two patients with INPPL1‐ related skeletal dysplasia diagnosed prenatally. A literature review is conducted to find out if high‐lethality is associated with particular pathogenic variants in INPPL1 gene. Prediction of lethality in the prenatal setting has an impact on perinatal management. Some frameshift variants in INPLL1 gene are uniquely observed in lethal cases; however, more patients are needed to confirm the correlation.

show abstract

Altered chondrocyte differentiation, matrix mineralization and MEK-Erk1/2 signaling in an INPPL1 catalytic knock-out mouse model of opsismodysplasia

Abstract: and its different differentiation steps. Finally, we identified a role of osteocalcin in mineralized nodules production and for the MEK-Erk1/2 signaling pathway in the OPS phenotype.

Cited by 7 publications

References 51 publications

IQGAP2 Inhibits Migration and Invasion of Gastric Cancer Cells via Elevating SHIP2 Phosphatase Activity

IQGAP2 Inhibits Migration and Invasion of Gastric Cancer Cells via Elevating SHIP2 Phosphatase Activity

Simultaneous testing of rule- and model-based approaches for runs of homozygosity detection opens up a window into genomic footprints of selection in pigs

Prenatal‐onset INPPL1‐related skeletal dysplasia in two unrelated families: Diagnosis and prediction of lethality

Contact Info

Product

Resources

About