Last update 19 Sep 2024

LAMA4

Last update 19 Sep 2024

Basic Info

Synonyms

LAMA3, LAMA4, laminin subunit alpha 4

+ [4]

Introduction

Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

Drugs associated with LAMA4

AG-101

Target

CD29 x EGFR x LAMA4

Mechanism

CD29 inhibitors [+2]

Active Org.

Arrogene, Inc.

Originator Org.

Cedars-Sinai Health System

Active Indication

Breast Cancer [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

2A3 mAb (Northwestern University)

Target

LAMA4

Mechanism

LAMA4 inhibitors

Active Org.

Northwestern University

Originator Org.

Northwestern University

Active Indication

Neovascularization, Pathologic

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LAMA4

100 Translational Medicine associated with LAMA4

0 Patents (Medical) associated with LAMA4

153

Literatures (Medical) associated with LAMA4

01 Sep 2024·Recent Patents on Anti-Cancer Drug Discovery

Comprehensive Genomic Analysis of Puerarin in Inhibiting Bladder Urothelial Carcinoma Cell Proliferation and Migration

Article

Author: Liu, Ying ; Shi, Zhen-Duo ; Wang, Jing-kai ; Zhang, Ge-jin ; Hao, Lin ; Liu, Peng-fei ; Pang, Kun ; Ding, Ji-cun ; Xu, Hao ; Xu, Peng ; Pan, Deng ; Ma, Yu-yang ; Wang, Hai-luo

Background:Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms.Methods:Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation.Results:A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218μmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patientsConclusion:Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

02 Aug 2024·Journal of Proteome Research

Extracellular Matrix Protein Signatures of the Outer and Inner Zones of the Rat Adrenal Cortex

Article

Author: Lotfi, Claudimara Ferini Pacicco ; Freitas, Danilo Henriques de Oliveira ; Auricino, Thais Barabba ; Kremer, Jean Lucas ; Palmisano, Giuseppe ; Bongiovani Rodrigues, Fernanda ; Santiago, Veronica Feijoli

This study analyzes the extracellular matrix (ECM) signatures of the outer (OF = capsule + subcapsular + zona glomerulosa cells) and inner fractions (IF = zona fasciculata cells) of the rat adrenal cortex, which comprise two distinct microenvironment niches. Proteomic profiles of decellularized OF and IF samples, male and female rats, identified 252 proteins, with 32 classified as ECM-component and ECM-related. Among these, 25 proteins were differentially regulated: 17 more abundant in OF, including Col1a1, Col1a2, Col6a1, Col6a2, Col6a3, Col12a1, Col14a1, Lama5, Lamb2, Lamc1, Eln, Emilin, Fbln5, Fbn1, Fbn2, Nid1, and Ltbp4, and eight more abundant in IF, including Col4a1, Col4a2, Lama2, Lama4, Lamb1, Fn1, Hspg2, and Ecm1. Eln, Tnc, and Nid2 were abundant in the female OF, while Lama2, Lama5, Lamb2, and Lamc1 were more abundant in the male IF. The complex protein signature of the OF suggests areas of tissue stress, stiffness, and regulatory proteins for growth factor signaling. The higher concentrations of Col4a1 and Col4a2 and their role in steroidogenesis should be further investigated in IF. These findings could significantly enhance our understanding of adrenal cortex functionality and its implications for human health and disease. Key findings were validated, and data are available in ProteomeXchange (PXD046828).

01 Jun 2024·Heliyon

An anoikis-related gene signature predicts prognosis, drug sensitivity, and immune microenvironment in cholangiocarcinoma

Article

Author: Feng, Zhijie ; He, Yujian ; Liu, Guochao ; Yin, Zhaoqiang

BackgroundCholangiocarcinoma is a malignant invasive biliary tract carcinoma with a poor prognosis. Anoikis-related genes are prognostic features of a variety of cancers. However, the value of prognostication and therapeutic effect of anoikis-related genes in cholangiocarcinoma have not been reported. The aim of this research was developing an ARGs signature associated with cholangiocarcinoma patients.MethodsWe introduced transcriptome data to discover genes that were differentially expressed in cholangiocarcinoma. Subsequently, WGCNA was utilized to screen critical module genes in reference to anoikis. The univariate Cox, Lasso regression and Kaplan-Meier survival were executed to build a prognostic signature. We further performed gene functional enrichment, immune microenvironment and immunotherapy analysis between two risk subgroups. Finally, the pRRophetic algorithm was applied to compare the half inhibitory concentration value of several drugs.ResultsA grand total of 1844 genes with differential expression related to the cholangiocarcinoma patients were identified. Furthermore, we obtained 2678 key module genes related to anoikis. Then, a prognostic signature was developed using the 6 prognostic genes (FXYD2, PCBD1, C1RL, GMNN, LAMA4 and HACL1). Independent prognostic analysis showed that risk score and alcohol could function as separate prognostic variables. We found cetain distinction in the immune microenvironment between the two risk subgroups. Moreover, immunotherapy evaluation showed that the anoikis-related gene signature could be applied as a therapy predictor. Finally, Chemotherapeutic drug sensitivity results showed that the low-risk group responded better to bosutinib, gefitinib, gemcitabine, and paclitaxel, while the high-risk group responded better to axitinib, cisplatin, and imatinib.ConclusionThe prognostic signature comprised of FXYD2, PCBD1, C1RL, GMNN, LAMA4 and HACL1 based on anoikis-related genes was established, which provided theoretical basis and reference value for the research and treatment of cholangiocarcinoma.

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LAMA4

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