Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility

• Published in: International journal of molecular sciences Vol. 22; no. 2; p. 626
• Main Authors: Lee, Hana, Kim, Won-Jin, Kang, Hyeon-Gu, Jang, Jun-Ho, Choi, Il Ju, Chun, Kyung-Hee, Kim, Seok-Jun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.01.2021; MDPI
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - physiopathology; Binding sites; Biomarkers; c-Jun protein; Cancer therapies; Cell growth; Cell Line, Tumor; cell motility; Cell Movement; Cell Proliferation; Datasets; Enzyme inhibitors; ERK/c-Jun/LAMB1 axis; Extracellular matrix; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Laminin; Laminin - genetics; Laminin - metabolism; Laminin - physiology; laminin subunit beta 1 (LAMB1); Liver cancer; MAP Kinase Signaling System; Medical prognosis; Metabolic pathways; Motility; Prognosis; Protein expression; Proteins; Proto-Oncogene Proteins c-jun - metabolism; Stomach Neoplasms - diagnosis; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - physiopathology; Transcription factors; cell motility; ERK/c-Jun/LAMB1 axis; cell proliferation; gastric cancer; laminin subunit beta 1 (LAMB1)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22020626

Gastric cancer is the fifth most common cancer worldwide with a poor survival rate. Therefore, it is important to identify predictive and prognostic biomarkers of gastric cancer. Laminin subunit beta 1 (LAMB1) is involved in attachment, migration, and organization during development, and its elevated expression has been associated with several cancers. However, the role and mechanism of LAMB1 in gastric cancer remains unknown. Here, we determined that LAMB1 is upregulated in gastric cancer tissues and contributes to cell growth and motility. Using a public database, we showed that LAMB1 expression was significantly upregulated in gastric cancer compared to normal tissues. LAMB1 was also found to be associated with poor prognosis in patients with gastric cancer. Overexpression of LAMB1 elevated cell proliferation, invasion, and migration; however, knockdown of LAMB1 decreased these effects in gastric cancer cells. U0126, an extracellular signal-regulated kinase (ERK) inhibitor, regulated the expression of LAMB1 in gastric cancer cells. Additionally, we showed that c-Jun directly binds to the LAMB1 promoter as a transcription factor and regulates its gene expression via the ERK pathway in gastric cancer cells. Therefore, our study indicates that LAMB1 promotes cell growth and motility via the ERK/c-Jun axis and is a potential biomarker and therapeutic target of gastric cancer.