Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Life Sci. 2019 Sep 15;233:116715. doi: 10.1016/j.lfs.2019.116715. Epub 2019 Jul 31.
PDZ and LIM domain protein 4 (PDLIM4) is frequently repressed in cancer tissues. However, the expression and role of PDLIM4 in ovarian cancer has not been addressed.
In this study, we examined the expression and prognostic significance of PDLIM4 in ovarian cancer. The function of PDLIM4 in ovarian cancer cell growth, invasion, and tumorigenesis was further explored.
PDLIM4 is downregulated in ovarian cancer compared to adjacent normal ovarian tissues. Downregulation of PDLIM4 is correlated with advanced tumor stage and lymph node metastasis. Low PDLIM4 expression is significantly associated with shorter overall survival in patients with ovarian cancer (P = 0.0136). Biologically, PDLIM4 overexpression suppresses the proliferation, colony formation, migration, and invasion of both CAOV3 and SKOV3 ovarian cancer cells, compared to empty vector-transfected cells. Consistently, in vivo data show that PDLIM4 overexpression inhibits the growth of SKOV3 xenograft tumors. Mechanistic investigation reveals that overexpression of PDLIM4 blocks the phosphorylation of STAT3 and represses STAT3-dependent transcriptional activation. Moreover, ectopic expression of PDLIM4 downregulates the expression of CCND1 and MMP9 in ovarian cancer cells. Rescue experiments demonstrate that overexpression of constitutively active STAT3 reverses PDLIM4-induced anticancer effects on ovarian cancer cells.
Overall, PDLIM4 downregulation is associated with aggressive tumor features and poor prognosis in ovarian cancer patients. PDLIM4 suppresses ovarian cancer cell growth and invasion by inhibiting STAT3 signaling. This study provides a potential therapeutic target for ovarian cancer.
PDZ 和 LIM 结构域蛋白 4（PDLIM4）在癌症组织中经常受到抑制。然而，PDLIM4 在卵巢癌中的表达和作用尚未得到解决。
在本研究中，我们研究了 PDLIM4 在卵巢癌中的表达和预后意义。进一步探讨了 PDLIM4 在卵巢癌细胞生长、侵袭和肿瘤发生中的功能。
与邻近正常卵巢组织相比，PDLIM4 在卵巢癌中下调。PDLIM4 的下调与晚期肿瘤分期和淋巴结转移相关。PDLIM4 低表达与卵巢癌患者总生存期缩短显著相关（P=0.0136）。在生物学上，与空载体转染细胞相比，PDLIM4 过表达可抑制 CAOV3 和 SKOV3 卵巢癌细胞的增殖、集落形成、迁移和侵袭。同样，体内数据表明 PDLIM4 过表达抑制 SKOV3 异种移植肿瘤的生长。机制研究表明，PDLIM4 过表达阻断 STAT3 的磷酸化并抑制 STAT3 依赖性转录激活。此外，PDLIM4 异位表达可下调卵巢癌细胞中 CCND1 和 MMP9 的表达。挽救实验表明，过表达组成型激活的 STAT3 可逆转 PDLIM4 对卵巢癌细胞的抗癌作用。
总体而言，PDLIM4 的下调与卵巢癌患者侵袭性肿瘤特征和不良预后相关。PDLIM4 通过抑制 STAT3 信号通路抑制卵巢癌细胞的生长和侵袭。本研究为卵巢癌提供了一个潜在的治疗靶点。
