Cullin 7 is a predictor of poor prognosis in breast cancer patients and is involved in the proliferation and invasion of breast cancer cells by regulating the cell cycle and microtubule stability

Oncol Rep. 2018 Feb;39(2):603-610. doi: 10.3892/or.2017.6106. Epub 2017 Nov 21.

Abstract

Cullin 7 is the 'scaffold' of the cullin-RING-based E3 ligases which catalyze the final step of the ubiquitination cascade in eukaryotic organisms. Although one study has reported the involvement of cullin 7 in the invasion and migration of breast cancer cells without further exploration of its mechanisms, the expression of cullin 7 in breast cancer tissues and its clinical significance have not been reported. The present study evaluated cullin 7 protein expression in malignant and benign breast tissues using immunochemistry, and further analyzed the association of positive cullin 7 expression in breast cancer tissues with clinicopathological characteristics of breast cancer patients. Cullin 7 expression was further silenced in breast cancer cells by siRNA and its functions and mechanisms in cell proliferation and invasion were investigated. The results showed that high cullin 7 expression was significantly correlated with pathological stage (P=0.013) and lymph node metastasis (P=0.022) of breast cancer. Patients with high cullin 7 expression had a shorter overall survival rate than those with low cullin 7 expression (P=0.037). Silencing of cullin 7 expression significantly inhibited the proliferation (P<0.05) and invasion (P<0.05), increased S1 phase (P<0.05), but decreased G2 phase (P<0.05) in MDA-MB-231 and BT549 cells. In addition, silencing of cullin 7 expression decreased cyclin A, but increased p21 protein expression. Moreover, silencing of cullin 7 expression altered the cell shape, caused disorder in microtubules, and increased the microtubule regeneration in MDA-MB-231 and BT549 cells. In conclusion, cullin 7 is overexpressed in breast cancer tissues which is associated with the development and prognosis of breast cancer. Cullin 7 is involved in the proliferation and invasion of breast cancer cells by regulating the cell cycle and microtubule stability.

MeSH terms

  • Animals
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Division*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cullin Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Mice
  • Microtubules / chemistry*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Prognosis
  • Up-Regulation*

Substances

  • CUL7 protein, human
  • Cullin Proteins