Inhibitory effect and mechanism of exogenous mammalian sterile 20-like kinase 1 on the growth of human colorectal cancer

Abstract

The present study aimed to observe the inhibitory effect and preliminary mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of colorectal cancer SW480 cells. The SW480 cells were randomly divided into the following groups: Control, empty enhanced green fluorescent protein (EGFP) plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 µmol/l fluorouracil (5-FU) and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell viability, Hoechst 33342 staining was used to observe cell apoptosis, and western blotting and immunohistochemistry were used to detect the levels of the proteins MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53 upregulated modulator of apoptosis (PUMA). In addition, nude mice were injected with SW480 cells to assess the tumor inhibition rates. Compared with the control group, the growth inhibition and apoptosis rates, the levels of MST1, p53 and PUMA, and the ratios of phospho-YAP1/YAP in the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were increased significantly (P<0.01). Additionally, relative to the control group, the tumor inhibition rates in the nude mice transplanted with SW480 cells of the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were 48.52±1.63 and 87.28±2.58%, respectively, and the positive rates of phospho-YAP1 (Ser127) protein in nuclei increased significantly (P<0.01). Overall, exogenous MST1 effectively inhibited the proliferation and growth of transplanted human colorectal cancer cells and promoted cancer cell apoptosis. The mechanism involved may be associated with the increase of intracellular phospho-YAP1 (Ser127) protein.

Downregulation of STK4 promotes colon cancer invasion/migration through blocking β‐catenin degradation

“…Gene therapy is an experimental strategy for colon cancer therapy with high efficiency [42]. STK4 acts as a tumor suppressor, and its overexpression inhibits tumor growth [21,43,44]. Our data also show that the change in STK4 levels negatively regulates β‐catenin‐mediated cell growth and cancer metastatic ability of colon cancer (Figs 2, 3A, and 5B).…”

Impact of Taurine on the proliferation and apoptosis of human cervical carcinoma cells and its mechanism

“…The Bcl2/Bax ratio is a classic indicator of apoptosis, and Bcl2/Bax plays an important role in the apoptosis of a variety of cells. [19]…”

“…Our recent studies [18,19] have found that regulating the MST1-Hippo signaling pathway can induce the apoptosis of lung cancer and colon cancer cells. Human mammalian sterile 20-like kinase 1 (MST1) is one of the core members of the Hippo pathway; the gene for MST1 is located on chromosome 20q11 and encodes a 59-K protein.…”

Manipulation of the gut microbiota by the use of prebiotic fibre does not override a genetic predisposition to heart failure

“…Several signalling pathways are responsible for apoptosis, including the gene coding for mammalian sterile 20-like kinase 1 (Mst1), an important mediator of cell death 8 , 9 . Mst1 has been largely studied in cancer biology, while little is known about its role in the pathophysiology of HF 10 – 12 . Mice with cardiac-specific overexpression of Mst1 have a phenotype consistent with HF due to dilated cardiomyopathy (DCM) 13 .…”