International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China; Department of general surgery, Changhai Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
Int J Cancer. 2014 Mar 15;134(6):1369-78. doi: 10.1002/ijc.28471. Epub 2013 Oct 3.
Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive growth, and is characterized by early tissue invasion and metastasis with poor prognosis. Identifying prognostic markers and delineating the underlying mechanisms that promote progression of PDAC are important for the treatment of pancreatic cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple processes during tumor development and metastasis. Here, we investigated the expression of TIP30 in PDAC and its prognostic value in PDAC patients. We examined the expression of TIP30 by immunohistochemistry in tissue microarrays containing 106 surgically resected PDAC. Kaplan-Meier analysis and Cox proportional hazards regression modeling analysis showed that TIP30 expression independently predicted better survival in pancreatectomy patients (p < 0.01). Moreover, decreased TIP30 expression was associated with lymph node metastasis (p < 0.05) and loss of E-cadherin expression (r = 0.329, p < 0.01). Suppression of TIP30 resulted in upregulation of Snail and subsequent downregulation of E-cadherin in SW1990 cells containing high-level of endogenous TIP30. However, in the PANC-1 cells containing low level of endogenous TIP30, suppressing TIP30 caused upregulation of Slug instead of Snail, followed by upregulation of MMP9 rather than E-cadherin. Taken together, our work reveals that decreased TIP30 expression is able to enhance invasion and metastasis of pancreatic cancer cells through upregulation of the Snail family members and may serve as an independent predictor for poor outcomes in PDAC patients.
胰腺导管腺癌（PDAC）以其侵袭性生长而闻名，其特征是早期组织浸润和转移，预后不良。鉴定预后标志物并阐明促进 PDAC 进展的潜在机制对于胰腺癌的治疗非常重要。TIP30 是一种新发现的肿瘤抑制因子，似乎参与了肿瘤发生和转移的多个过程。在这里，我们研究了 TIP30 在 PDAC 中的表达及其对 PDAC 患者的预后价值。我们通过免疫组织化学方法在包含 106 例手术切除的 PDAC 的组织微阵列中检测 TIP30 的表达。Kaplan-Meier 分析和 Cox 比例风险回归模型分析表明，TIP30 的表达独立预测了胰切除术患者的更好生存（p < 0.01）。此外，TIP30 表达降低与淋巴结转移（p < 0.05）和 E-钙粘蛋白表达缺失相关（r = 0.329，p < 0.01）。在含有高水平内源性 TIP30 的 SW1990 细胞中，抑制 TIP30 导致 Snail 的上调和随后的 E-钙粘蛋白的下调。然而，在含有低水平内源性 TIP30 的 PANC-1 细胞中，抑制 TIP30 导致 Slug 而不是 Snail 的上调，随后 MMP9 而不是 E-钙粘蛋白的上调。总之，我们的工作表明，TIP30 表达的降低能够通过上调 Snail 家族成员增强胰腺癌细胞的侵袭和转移能力，并且可能作为 PDAC 患者不良预后的独立预测因子。
