Overexpression of Cullin1 is associated with poor prognosis of patients with gastric cancer.

Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cullin1 in the development of gastric cancer, we examined the expression of Cullin1 in primary gastric cancer tissues and analyzed the correlation between Cullin1 expression and clinicopathologic variables and patients survival. We constructed a tissue microarray that includes 792 primary gastric cancer tissues and evaluated the Cullin1 expression by immunohistochemistry in the tumor biopsies. We also studied the role of Cullin1 in gastric cancer cell proliferation and adhesion by performing sulforhodamine B cell proliferation assay and cell attachment assay. The Cullin1 overexpression was significantly correlated with gastric cancer TNM stage (P = .011), depth of invasion (P = .035, comparing T1-T3 versus T4), and lymph node metastasis (P = .036). Furthermore, we showed a strong correlation between high Cullin1 expression and worse overall and 3-year survival rates in gastric cancer patients (P = .042 and P = .026, respectively). Cox regression analysis revealed that Cullin1 expression was an independent prognostic factor to predict 3-year patient outcome in gastric cancer (P = .028). Finally, we found that Cullin1 knockdown inhibits cell growth by up-regulating p27 expression and decreases cell adhesion ability by suppressing the expression of Src family kinases and focal adhesion kinase. Our data indicated that Cullin1 may be an important marker for human gastric cancer lymph node metastasis and prognosis.