LATS1 suppresses proliferation and invasion of cervical cancer

Abstract

Loss of large tumor suppressor kinase 1 (LATS1)Y has been implicated in numerous types of human cancer. However, its involvement in human cervical cancer remains to be elucidated. The present study aimed to investigate the clinical significance and biological characteristics of LATS1 in human cervical cancer. The present study investigated the protein expression levels of LATS1 in tissues from 80 cases of cervical cancer using immunohistochemistry and demonstrated that LATS1 was downregulated in 45% (36/80) of cervical cancers. Transfection of LATS1 was performed in the SiHa cell line and LATS1 siRNA knockdown was performed in the Caski cell line. MTT assay and Matrigel invasion assay indicated that LATS1 overexpression inhibited cell proliferation and invasion. LATS1 overexpression upregulated p27 expression, and downregulated the expression of cyclin E and matrix metalloproteinase 9. In addition, LATS1 overexpression stimulated yes‑associated protein 1 (YAP) phosphorylation. Depletion of LATS1 in Caski cells resulted in the opposite effects. The current study demonstrated that LATS1 was downregulated in cervical cancer and may suppress cell growth and invasion through regulating the expression of cyclin E, p27, MMP9 and YAP.

Figure 1.

Expression of LATS1 protein in cervical cancer tissues. (A) Strong LATS1 expression in normal cervical tissue. (B) Positive LATS1 expression in a case of stage II cervical cancer. (C) Negative staining of LATS1 in a case of stage III cervical cancer. (D) Weak LATS1 expression in a case of stage I adenocarcinoma. Magnification, ×400. LATS1, large tumor suppressor kinase 1.

Figure 2.

LATS1 transfection efficiency in cervical cancer cell lines. (A) Western blot analysis demonstrated strong LATS1 expression in the Caski cell line and weak LATS1 expression in the SiHa cell line. (B) Western blot analysis demonstrated that LATS1 transfection in SiHa cells upregulated LATS1 protein expression, and siRNA knockdown in Caski cells downregulated LATS1 protein expression, compared with controls. LATS1, large tumor suppressor kinase 1; siRNA, small interfering RNA.

Figure 3.

LATS1 inhibits proliferation and invasion of cervical cancer cells. (A) MTT assay demonstrated that LATS1 transfection significantly reduced cell proliferation in the SiHa cell line (*P<0.05 vs. empty plasmid control), while LATS1 knockdown significantly increased cell proliferation in the Caski cell line (*P<0.05 vs. negative siRNA control). (B) Matrigel invasion assay demonstrated that LATS1 transfection in SiHa cells significantly decreased the number of invading cells (*P<0.05 vs. empty plasmid control), while LATS1 knockdown in Caski cells significantly increased the invasiveness of Caski cells (*P<0.05 vs. negative siRNA control). LATS1, large tumor suppressor kinase 1; siRNA, small interfering RNA.

Figure 4.

LATS1 inhibits cervical cancer cell proliferation and invasion via regulation of cyclin E, p27, MMP9, YAP and CTGF. (A) Western blot analysis demonstrated that LATS1 transfection downregulated the levels of cyclin E and MMP9, and upregulated p27 expression in SiHa cells compared with the control. LATS1 knockdown in Caski cells upregulated cyclin E and MMP9, and downregulated p27 expression. (B) LATS1 overexpression in SiHa cells decreased YAP and CTGF protein levels, and increased YAP phosphorylation compared with the control. LATS1 knockdown in Caski cells resulted in the opposite effects, which upregulated YAP and downregulated p-YAP. LATS1, large tumor suppressor kinase 1; MMP9, matrix metalloproteinase 9; YAP, yes associated protein 1; p-YAP, phosphorylated YAP; CTGF, connective tissue growth factor; siRNA, small interfering RNA.