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Laminins are crucial proteins in the basal lamina, and these form a protein network that influences both normal and transformed cell differentiation, migration and adhesion, as well as phenotype and survival. Several studies in cancers have shown that the elevated expression of LAMC2 on cancer cells appears to drive tumorigenesis through its interactions with several cell-surface receptors including several integrins and EGFRs. Accumulating evidence indicated that LAMC2-mediated signaling network plays an important role in the progression, migration and invasion of multiple types of cancer, suggesting that it might be a potential therapeutic anticancer target for inhibiting tumorigenesis. Furthermore, elevated serum levels of LAMC2 in cancer patients might appear as attractive serum-based diagnostic biomarker.
Fig. 1. Schematic illustrations of Laminin-332 structure: Laminin-332 forms a cruciform shaped structure consisting of three chains (alpha3, beta3 and gamma2, also known as LAMC2). (Garg et al, 2014)
It is universally acknowledged that lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. Researchers identified LAMC2 to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT), while LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, along with attenuated metastasis in mice. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. These findings, taken together, suggested that LAMC2 may promote metastasis in lung adenocarcinoma via EMT and could be a potential therapeutic target.
In another study, given that non-small cell lung cancer (NSCLC) lacks reliable serological biomarkers for predicting patients' survival and response to treatment, researchers conducted a study to examine the capability of serum LAMC2 and four known tumor markers for disease prognosis and patients' risk stratification. LAMC2, CA 125, CEA, CYFRA 21-1 and SCC levels were retrospectively measured. LAMC2 showed significant prognostic ability for overall survival in the full cohort. LAMC2 and CYFRA 21-1 combination enhanced prognostic models based on common clinical parameters, further enabling stratification of patients into clear risk groups. Thus this study indicated LAMC2 as a novel NSCLC prognostic factor. LAMC2 combined with CA 125 and CYFRA 21-1 could aid in clinical prediction of NSCLC patients' overall survival and inform clinical practice.
In search of the effective diagnostic, prognostic and disease-monitoring biomarkers for pancreatic ductal adenocarcinoma (PDAC), researchers identified a total of 2,190 non-redundant proteins in four PDAC tissues and their adjacent benign tissues. results showed a significant elevation of LAMC2 in pancreatic cancer serum. Extensive validation of LAMC2 in healthy, benign, and PDAC sera from geographically diverse cohorts demonstrated a significant increase in levels in early-stage PDAC compared to benign diseases. The combination of LAMC2 and CA19.9 improved the individual diagnostic performance in distinguishing healthy and benign subjects from PDAC. Additionally, LAMC2 was positive in about 60% of patients with PDAC who had no CA19.9 elevation. Thus it was concluded that LAMC2 is a new serum biomarker for pancreatic adenocarcinoma.
To evaluate the effects of SNPs (single nucleotide polymorphisms) on CRC (colorectal cancer) susceptibility in Chinese populations, researchers screened out all potentially functional SNPs in exons of lncRNAs (long non-coding RNA) located in CRC susceptibility loci. Analysis showed that CG and GG genotypes of the rs2147578 were significantly associated with increased risk for CRC occurrence. Bioinformatics analyses showed that rs2147578 is located in the transcript of lnc-LAMC2-1:1 and could influence the binding of lnc-LAMC2-1:1/miR-128-3p. Further analysis showed that rs2147578 is correlated with the expression of a well-established oncogene LAMC2. These findings indicated that rs2147578 in lnc-LAMC2-1:1 might be a genetic modifier for the development of CRC.