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

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 elevate...

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Main Authors: Hana Lee, Won-Jin Kim, Hyeon-Gu Kang, Jun-Ho Jang, Il Ju Choi, Kyung-Hee Chun, Seok-Jun Kim
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/2/626
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author Hana Lee
Won-Jin Kim
Hyeon-Gu Kang
Jun-Ho Jang
Il Ju Choi
Kyung-Hee Chun
Seok-Jun Kim
author_facet Hana Lee
Won-Jin Kim
Hyeon-Gu Kang
Jun-Ho Jang
Il Ju Choi
Kyung-Hee Chun
Seok-Jun Kim
author_sort Hana Lee
collection DOAJ
description 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.
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spelling doaj.art-908280848564424eba535060be0accd52023-12-03T12:39:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122262610.3390/ijms22020626Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and MotilityHana Lee0Won-Jin Kim1Hyeon-Gu Kang2Jun-Ho Jang3Il Ju Choi4Kyung-Hee Chun5Seok-Jun Kim6Department of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju 61452, KoreaDepartment of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju 61452, KoreaDepartment of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju 61452, KoreaDepartment of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju 61452, KoreaCenter for Gastric Cancer, National Cancer Center Research Institute, Goyang 10408, KoreaDepartment of Biochemistry & Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDepartment of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju 61452, KoreaGastric 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.https://www.mdpi.com/1422-0067/22/2/626laminin subunit beta 1 (LAMB1)gastric cancercell proliferationcell motilityERK/c-Jun/LAMB1 axis
spellingShingle Hana Lee
Won-Jin Kim
Hyeon-Gu Kang
Jun-Ho Jang
Il Ju Choi
Kyung-Hee Chun
Seok-Jun Kim
Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility
International Journal of Molecular Sciences
laminin subunit beta 1 (LAMB1)
gastric cancer
cell proliferation
cell motility
ERK/c-Jun/LAMB1 axis
title Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility
title_full Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility
title_fullStr Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility
title_full_unstemmed Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility
title_short Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility
title_sort upregulation of lamb1 via erk c jun axis promotes gastric cancer growth and motility
topic laminin subunit beta 1 (LAMB1)
gastric cancer
cell proliferation
cell motility
ERK/c-Jun/LAMB1 axis
url https://www.mdpi.com/1422-0067/22/2/626
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