Cancer/testis antigen LDHC promotes proliferation and metastasis by activating the PI3K/Akt/GSK-3β-signaling pathway and the in lung adenocarcinoma

Journal Article · Fri Jan 15 04:00:00 EST 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2020.112414· OSTI ID:23195400

Chen, Liangyuan ^[1]; Wu, Qiumei ^[1]; Xu, Xunyu ^[2]; Yang, Caihong; You, Jianbin; Chen, Falin; Zeng, Yanfen ^[1]

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1. Department of Clinical Laboratory, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou (China)
2. Department of Thoracic Surgery, Fujian Provincial Hospital, Shengli Clinical College of Fujian Medical University, Fuzhou (China)

The cancer/testis antigen lactate dehydrogenase-C4 (LDHC) is a specific isoenzyme of the LDH family that regulates invasion and metastasis in some malignancies; however, little is known regarding its role in progression of lung adenocarcinoma (LUAD). Thus, we investigated LDHC expression by immunohistochemistry, and analyzed its clinical significance in 88 LUAD specimens. The role and molecular mechanisms subserving LDHC in cellular proliferation, migration, and invasion were explored both in vitro and in vivo. As a result, we found that high LDHC expression was significantly correlated with clinicopathological features of aggressive LUAD and a poor prognosis. Overexpression of LDHC induced LUAD cells to produce lactate and ATP, increased their metastatic and invasive potential—, and accelerated xenograft tumor growth. We further demonstrated that overexpression of LDHC affected the expression of cell proliferation-related proteins (cyclin D1 and c-Myc) and epithelial-mesenchymal transition (EMT)-related proteins (MMP-2, MMP-9, E-cadherin, Vimentin, Twist, Slug, and Snail) both in vitro and in vivo. Finally, excessive activation of LDHC enhanced the phosphorylation levels of AKT and GSK-3β, revealing activation of the PI3K/Akt/GSK-3β oncogenic-signaling pathways. Treatment with a PI3K inhibitor reversed the effects of LDHC overexpression by inhibiting cellular proliferation, migration, and invasion, with diminished levels of p-Akt and p-GSK3β. PI3K inhibition also reversed cell proliferation-related and EMT-related proteins in LDHC-overexpressing A549 cells. In conclusion, LDHC promotes proliferation, migration, invasion, and EMT in LUAD cells via activation of the PI3K/Akt/GSK-3β pathway.

• OSTI ID: 23195400
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 398; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIGENS
ATP
CARCINOMAS
CELL PROLIFERATION
IN VITRO
IN VIVO
ISOENZYMES
LACTATE DEHYDROGENASE
LACTATES
LUNGS
METASTASES
PHOSPHORYLATION
SNAILS
TESTES