LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton

Bozal-Basterra, Laura; Gonzalez-Santamarta, María; Muratore, Veronica; Martín-Martín, Natalia; Ercilla, Amaia; Rodríguez, José Antonio; Carracedo, Arkaitz; Sutherland, James D.; Barrio, Rosa

doi:10.3389/fcell.2021.624089

Cited by 13 publications

(15 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We performed network analysis using IPA on the list of differentially expressed proteins in both the diffuse and intestinal subtypes of gastric cancer. IPA network analysis of the diffuse subtype showed upregulation of proteins like HSPB1 [ 37 , 38 ], KCTD [ 39 , 40 , 41 , 42 ], TPM3 [ 43 , 44 , 45 , 46 ], PDLIM7 [ 47 , 48 , 49 ], LUZP1 [ 50 ], ACTN1 [ 51 , 52 ], and CFL2 [ 53 ], which have oncogenic properties in the topmost network ( Supplementary Figure S1 ). These proteins are involved in promoting tumor growth, invasion and resistance to anti-tumor therapy in various cancers including gastric cancer.…”

Section: Resultsmentioning

confidence: 99%

Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer

Singh

Bhat

Sathe

et al. 2021

Cancers

View full text Add to dashboard Cite

Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7448 or 4846 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma-associated antigen 9 (MAGE-A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer

Singh

Bhat

Sathe

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…It remains unknown why cells have the unnecessary delay in contraction during cytokinesis via LUZP1. Recent studies have reported that LUZP1 expression is downregulated in several types of cancer and that LUZP1 can suppress the proliferation of some cancer cells (Dong et al, 2021; Bozal-Basterra et al, 2021). These findings suggest that LUZP1 may contribute to genome stability by preventing a failed chromosome distribution by delaying cytokinesis.…”

Section: Discussionmentioning

confidence: 99%

“…The timing and location of protein activation and inactivation during cell division are highly regulated by post-translational modifications, such as protein phosphorylation and ubiquitination, to ensure the accurate progression of cell division (Lara- Gonzalez et al, 2021;Nasa et al, 2018;Vagnarelli, 2021). The chromosomal passenger complex (CPC) is an essential kinase complex for mitosis and is required for various mitotic events, such as chromosome condensation, kinetochore-microtubule attachment, spindle assembly checkpoint, cleavage furrow ingression, and abscission (Carmena et Salaun et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…1A; Lee et al, 2001; Sun et al, 1996; Wang and Nakamura, 2019). The protein function of LUZP1 has long been unknown, but it is becoming rapidly apparent: LUZP1 mainly localizes to the actin filaments and stabilizes the actin cytoskeleton (Gonçalves, 2022; Wang and Nakamura, 2019); LUZP1 localizes at the centrosome and restricts primary cilia formation (Bozal-Basterra et al, 2020; Gonçalves et al, 2020); embryos of LUZP1 null knockout (KO) mice display cardiovascular and cranial defects with prenatal death (Hsu et al, 2008); LUZP1 genomic aberrations are detected in several types of cancer and syndromes (Bhat et al, 2022; Bozal-Basterra et al, 2021; Dong et al, 2021; Edwards et al, 2019; Poel et al, 2019; Zaveri et al, 2014); And LUZP1 interacts with microtubule and various other proteins and complexes (Fig. 1A; Krebs et al, 2010; Liu et al, 2017; Niri et al, 2021; Yano et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LUZP1 regulates the constriction velocity of the contractile ring during cytokinesis

Hyodo

Asano-Inami

Ito³

et al. 2022

Preprint

View full text Add to dashboard Cite

There has been a great deal of research on cell division and its mechanisms; however, its processes have not yet been entirely elucidated. To find novel proteins that regulate cell division, we performed the screening using siRNAs and/or the expression plasmid of the target genes and identified leucine zipper protein 1 (LUZP1). Recent studies have shown that LUZP1 interacts with various proteins and stabilizes the actin cytoskeleton; however, the function of LUZP1 in mitosis is not known. In this study, we found that LUZP1 colocalized with the chromosomal passenger complex (CPC) at the centromere in metaphase and at the central spindle/midbody in anaphase and that these LUZP1 localizations were regulated by CPC activity and kinesin family member 20A (KIF20A). Mass spectrometry analysis identified that LUZP1 interacted with death-associated protein kinase 3 (DAPK3), one regulator of the cleavage furrow ingression in cytokinesis. In addition, we found that LUZP1 also interacted with myosin light chain 9 (MYL9), a substrate of DAPK3, and comprehensively inhibited MYL9 phosphorylation by DAPK3. In line with a known role for MYL9 in the actin-myosin contraction, LUZP1 suppression accelerated the constriction velocity at the division plane in our timelapse analysis. Our study indicates that LUZP1 is a novel regulator for cytokinesis that regulates the constriction velocity of the contractile ring.

show abstract

“…19503-1-AP, 1:100; Proteintech, Wuhan, China) ( 31 ) and TUBG1 (Cat No. 15176-1-AP, 1:100; Proteintech, Wuhan, China) ( 32 ). Two pathologists observed the results.…”

Section: Methodsmentioning

confidence: 99%

Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma

et al. 2022

View full text Add to dashboard Cite

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, its carcinogenic mechanism is still unclear, looking for both diseases’ transcriptome levels, the same changes as we are looking for NAFLD may provide a potential mechanism of action of HCC. Thus, our study aimed to discover the coexisting pathogenic genes of NAFLD and HCC.MethodsWe performed a variance analysis with public data for both diseases. At the same time, weighted gene correlation network analysis (WGCNA) was used to find highly correlated gene modules in both diseases. The darkturquoise gene module was found to be highly correlated with both diseases. Based on the diagnosis related module genes and the differential genes of the two diseases, we constructed diagnostic and prognostic models by logistic regression, univariate Cox regression, and LASSO regression. Public datasets verified the results. Meanwhile, we built a competing endogenous RNA (ceRNA) network based on the model genes and explored the related pathways and immune correlation involved in the two diseases by using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Immunohistochemistry was used to verify the different expression of ABCC5 and TUBG1 among the normal liver, NAFLD, and HCC tissues. Sodium palmitate/sodium oleate was used to establish high-fat cell models, and Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify the messenger RNA (mRNA) expression of ABCC5 in lipidization cells.ResultsA total of 26 upregulated genes and 87 downregulated genes were found using limma package identification analysis. According to WGCNA, the darkturquoise gene module was highly correlated with the prognosis of both diseases. The coexisting genes acquired by the two groups were only three central genes, that is, ABCC5, DHODH and TUBG1. The results indicated that the diagnostic and prognostic models constructed by ABCC5 and TUBG1 genes had high accuracy in both diseases. The results of immunohistochemistry showed that ABCC5 and TUBG1 were significantly overexpressed in NAFLD and HCC tissues compared with normal liver tissues. The Oil Red O staining and triglyceride identified the successful construction of HepG2 and LO2 high-fat models using PA/OA. The results of RT-qPCR showed that the lipidization of LO2 and HepG2 increased the mRNA expression of ABCC5.ConclusionsThe gene model constructed by ABCC5 and TUBG1 has high sensibility and veracity in the diagnosis of NAFLD as well as the diagnosis and prognosis of HCC. ABCC5 and TUBG1 may play an important role in the development of NAFLD to HCC. In addition, lipidization could upregulate the mRNA expression of ABCC5 in HCC.

show abstract

LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton

Cited by 13 publications

References 59 publications

Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer

Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer

LUZP1 regulates the constriction velocity of the contractile ring during cytokinesis

Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma

Contact Info

Product

Resources

About