STYK1 promotes epithelial-mesenchymal transition and tumor metastasis in human hepatocellular carcinoma through MEK/ERK and PI3K/AKT signaling

Abstract

Serine/threonine/tyrosine kinase 1 (STYK1) is known to be involved in tumor progression. However, its molecular role and mechanism in hepatocellular carcinoma (HCC) remains unknown. We evaluated the effect of STYK1 expression in HCC tissues and investigated the underlying mechanisms associated with progression. HCC tissues expressed greater levels of STYK1 than paired non-tumor tissues. Patients with HCC expressing low levels of STYK1 showed both, greater disease-free (p < 0.0001) and overall (p = 0.0004) survival than those expressing high levels of STYK1. Decreased expression of STYK1 was significantly associated with decreased cell proliferation, reduced migratory capability, and reduced invasive capability. Overexpression of STYK1 was significantly associated with increased cell proliferation, migratory capability, and invasive capability in vitro, as well as increased volume of tumor, weight of tumor, and number of pulmonary metastases in vivo. Furthermore, STYK1’s mechanism of promoting cancer cell mobility and epithelial-mesenchymal transition (EMT) was found to be via the MEK/ERK and PI3K/AKT pathways, resulting in increased expression of mesenchymal protein markers: snail, fibronectin, and vimentin, and decreased E-cadherin expression. Our results suggest that STYK1 acts as an oncogene by inducing cell invasion and EMT via the MEK/ERK and PI3K/AKT signaling pathways and it therefore may be a potential therapeutic target in HCC.

ZC3H13 suppresses colorectal cancer proliferation and invasion via inactivating Ras–ERK signaling

“…Previous studies had confirmed inactivation of ERK signaling pathway could induce suppression of Snail, Cyclin D1, and Cyclin E1, as well as increase of Occludin and Zo-1 (Bai et al, 2017;Iacovelli et al, 2007;S. O. Kim & Kim, 2013;Wang et al, 2016), which were consistent with what we have found. Luo et al (2009) had indicated that ZC3H13 may interact with Kras, which was a canonical upstream factor of ERK signaling pathway (Toulany et al, 2016;Wakamatsu et al, 2008;Xian et al, 2016).…”

Styk1 expression is a hallmark of murine NK cells and other NK1.1+ subsets but is dispensable for NK‐cell development and effector functions

“…A pioneer study showed in stably expressing cell lines that Styk1 could concomitantly activate both MAP kinase and PI3K pathways [11]. This initial report was followed by other observations that confirmed activation of PI3K/Akt by Styk1 in other cell lines [18,31,32]. Styk1 overexpression leads to an increased glycolytic capacity, and decreases oxidative phosphorylation via PI3K/Akt induction [33].…”

NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality

“…For a deeper research, we studied two EMT-related protein, fibronectin and claudin-1, and their mRNA expression level in order to reveal the mechanism. Fibronectin is a mesenchymal biomarker [11,24] with the same significance of vimentin and N-cadherin. Claudin-1 expresses by epithelial tissue [10], similarly to E-cadherin.…”

“…Finally, we chose two EMT-related biomarkers, claudin-1 and fibronectin. Claudin-1 is considered as epithelial marker [10], and fibronectin is a mesenchymal one [11]. Upregulation of NFAT5 suppressed fibronectin expression, in the mean while induced expression of claudin-1 in hyperosmotic solution ( Figure 5A).…”