LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis

Fu, Tao; Liu, Junxia; Xie, Juan; Gao, Zhen; Yang, Zhenshan

doi:10.1136/bmjopen-2022-063682

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…LAMC2 is a subunit of the heterotrimeric glycoprotein laminin-332, which is a fundamental component of epithelial basement membranes and regulates cell motility and adhesion [41]. High LAMC2 expression correlates with poorer survival in multiple cancers including thyroid, NSCLC, and cholangiocarcinoma [46,47]. Our data suggest that LAMC2 expression is directly regulated by CTGF, as shown by the significant increase in LAMC2 expression in cells lacking CTGF and the downregulation of LAMC2 expression following exposure to rCTGF.…”

Section: Discussionmentioning

confidence: 56%

“…In ovarian cancer, molecular subgroups of HGSOC established by the TCGA identified a "mesenchymal" subgroup signature [49], which has been associated with the overexpression of EMT markers, the lowest rates of optimal surgical debulking, and worse OS [50,51]. LAMC2 expression was correlated with worse survival, lymph node metastasis, tumornode-metastasis stages, and tumor status [46]. There are contradictory reports on the effect of CTGF in various malignancies [52][53][54][55][56].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

Gogoi,

Galoforo,

Fox

et al. 2023

Cancers

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Background: Epithelial–mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between the epithelial and mesenchymal stage is essential for tissue homeostasis. Many of the genes promoting mesenchymal transformation have been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify the genes responsible for maintaining the epithelial phenotype and inhibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expression was determined via qPCR and Western blot analysis. The knockout of CTGF was completed using the CTGF sgRNA CRISPR/CAS9. The tumorigenic potential was determined using NCG mice. Results: The knockout of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as anoikis resistance, cytoskeleton remodeling, increased cell stiffness, and the acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with the early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for the conservation of epithelial structure and function. These findings provide a new window into understanding the early stages of mesenchymal transformation.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

Gogoi,

Galoforo,

Fox

et al. 2023

Cancers

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“…Recent investigations have analyzed that the LAMC2 is increased in multiple types of cancer and is involved in promoting the advancement of tumors (Erice et al 2023 ; Ferreira et al 2022 ; Fu et al 2022 ). Besides, to investigate the biological functions of LAMC2 in GC, stable LAMC2 knockdown and overexpression cell lines were generated.…”

Section: Discussionmentioning

confidence: 99%

LAMC2 regulates the proliferation, invasion, and metastasis of gastric cancer via PI3K/Akt signaling pathway

Cheng,

Li,

Dong

et al. 2024

J Cancer Res Clin Oncol

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Objectives Gastric cancer (GC) is a prevalent malignant tumor widely distributed globally, exhibiting elevated incidence and fatality rates. The gene LAMC2 encodes the laminin subunit gamma-2 chain and is found specifically in the basement membrane of epithelial cells. Its expression is aberrant in multiple types of malignant tumors. This research elucidated a link between LAMC2 and the clinical characteristics of GC and investigated the potential involvement of LAMC2 in GC proliferation and advancement. Materials and methods LAMC2 expressions were detected in GC cell lines and normal gastric epithelial cell lines via qRT-PCR. Silencing and overexpression of the LAMC2 were conducted by lentiviral transfection. A xenograft mouse model was also developed for in vivo analysis. Cell functional assays were conducted to elucidate the involvement of LAMC2 in cell growth, migration, and penetration. Further, immunoblotting was conducted to investigate the impact of LAMC2 on the activation of signal pathways after lentiviral transfection. Results In the findings, LAMC2 expression was markedly upregulated in GC cell lines as opposed to normal gastric epithelial cells. In vitro analysis showed that sh-LAMC2 substantially inhibited GC cell growth, migration, and invasion, while oe-LAMC2 displayed a contrasting effect. Xenograft tumor models demonstrated that oe-LAMC2 accelerated tumor growth via high expression of Ki-67. Immunoblotting analysis revealed a substantial decrease in various signaling pathway proteins, PI3K, p-Akt, and Vimentin levels upon LAMC2 knockdown, followed by increased E-cadherin expression. Conversely, its overexpression exhibited contrasting effects. Besides, epithelial-mesenchymal transition (EMT) was accelerated by LAMC2. Conclusion This study provides evidence indicating that LAMC2, by stimulating signaling pathways, facilitated EMT and stimulated the progression of GC cells in laboratory settings and mouse models. Research also explored that the abnormal LAMC2 expression acts as a biomarker for GC.

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“…Platelet derived growth factor beta (PDGFB), fibroblast growth factor 1 (FGF1), laminin subunit gamma 2 (LAMC2), integrin beta subunit 6 (ITGB6) and Ephrin A3 (EFNA3) encode respective receptors involved in cell-extracellular matrix (ECM) signaling, which plays a positive role in cancer initiation and progression mainly through induction of EMT transcription factors that increase cell motility and promote cell migration [57][58][59][60][61][62][63].…”

Section: Pdgfbmentioning

confidence: 99%

Hypoxia Modulates Radiosensitivity and Response to Different Radiation Qualities in A549 Non-Small Cell Lung Cancer (NSCLC) Cells

Nisar,

Labonté,

Roggan

et al. 2024

IJMS

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Hypoxia-induced radioresistance reduces the efficacy of radiotherapy for solid malignancies, including non-small cell lung cancer (NSCLC). Cellular hypoxia can confer radioresistance through cellular and tumor micro-environment adaptations. Until recently, studies evaluating radioresistance secondary to hypoxia were designed to maintain cellular hypoxia only before and during irradiation, while any handling of post-irradiated cells was carried out in standard oxic conditions due to the unavailability of hypoxia workstations. This limited the possibility of simulating in vivo or clinical conditions in vitro. The presence of molecular oxygen is more important for the radiotoxicity of low-linear energy transfer (LET) radiation (e.g., X-rays) than that of high-LET carbon (12C) ions. The mechanisms responsible for 12C ions’ potential to overcome hypoxia-induced radioresistance are currently not fully understood. Therefore, the radioresistance of hypoxic A549 NSCLC cells following exposure to X-rays or 12C ions was investigated along with cell cycle progression and gene expression by maintaining hypoxia before, during and after irradiation. A549 cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h and then irradiated with X-rays (200 kV) or 12C ions (35 MeV/n, LET ~75 keV/µm). Cell survival was evaluated using colony-forming ability (CFA) assays immediately or 24 h after irradiation (late plating). DNA double-strand breaks (DSBs) were analyzed using γH2AX immunofluorescence microscopy. Cell cycle progression was determined by flow cytometry of 4′,6-diamidino-2-phenylindole-stained cells. The global transcription profile post-irradiation was evaluated by RNA sequencing. When hypoxia was maintained before, during and after irradiation, hypoxia-induced radioresistance was observed only in late plating CFA experiments. The killing efficiency of 12C ions was much higher than that of X-rays. Cell survival under hypoxia was affected more strongly by the timepoint of plating in the case of X-rays compared to 12C ions. Cell cycle arrest following irradiation under hypoxia was less pronounced but more prolonged. DSB induction and resolution following irradiation were not significantly different under normoxia and hypoxia. Gene expression response to irradiation primarily comprised cell cycle regulation for both radiation qualities and oxygen conditions. Several PI3K target genes involved in cell migration and cell motility were differentially upregulated in hypoxic cells. Hypoxia-induced radioresistance may be linked to altered cell cycle response to irradiation and PI3K-mediated changes in cell motility and migration in A549 cells rather than less DNA damage or faster repair.

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LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis

Cited by 9 publications

References 37 publications

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

LAMC2 regulates the proliferation, invasion, and metastasis of gastric cancer via PI3K/Akt signaling pathway

Hypoxia Modulates Radiosensitivity and Response to Different Radiation Qualities in A549 Non-Small Cell Lung Cancer (NSCLC) Cells

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