Keratin 18 induces proliferation, migration, and invasion in gastric cancer via the MAPK signalling pathway

• Published in: Clinical and experimental pharmacology & physiology 2021-01, Vol.48 (1), p.147-156
• Main Authors: Wang, Peng‐Bin, Chen, Yan, Ding, Guang‐Rong, Du, Hong‐Wei, Fan, Hong‐Yan
• Format: Article
• Language: English
• Subjects: Apoptosis; Cancer; Cell migration; Cell proliferation; Cytoskeleton; Gastric cancer; Immunohistochemistry; Keratin; KRT18; malignant behaviour; MAP kinase; MAPK; Prognosis; Proteins; Signal transduction; Signaling; siRNA; Tissues
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13401

Purpose Keratin 18 (KRT18) is a cytoskeleton protein that plays a key role in multiple cancers. The present study aims to further investigate the roles of KRT18 in gastric cancer (GC) tissues and cells. Methods The KRT18 protein expression levels of GC tissues and cells were detected using immunohistochemistry and western blot. The relationship between KRT18 expression levels and the prognosis of GC patients was further analyzed. To explore this relationship, small interfering RNA (siRNA) was used to inhibit the endogenous expression of KRT18 in GC cells. Furthermore, the effects of KRT18 on the proliferation, invasion, migration, and apoptosis of GC cells were analyzed in vitro. In addition, the role of KRT18 in GC‐specific processes was investigated. Results Keratin 18 expression was shown to be up‐regulated in GC tissues and associated with poor prognosis. Following KRT18 silencing with siRNA, the proliferation, invasion, and migration ability of GC cells were significantly inhibited, while the apoptotic process was promoted. Furthermore, the activation of the MAPK signalling pathway was identified as the potential mechanism through which KRT18 influenced GC processes. Conclusions Keratin 18 plays a cancer‐promoting role and might be a potential therapeutic target in the treatment of GC. In the process of gastric cancer, the abnormally high expression of Keratin 18 promotes proliferation, apoptosis resistance, invasion and migration of tumour cell via the MAPK signal pathway.