Fibrillin-1, induced by Aurora-A but inhibited by BRCA2, promotes ovarian cancer metastasis

Abstract

While Aurora-A (Aur A) provokes, BRCA2 restrains primary tumorigenesis, the roles of Aur A and BRCA2 in cancer metastasis remains unclear. Here, we show that the metastatic promoting markers SLUG, FBN1, and MMP2, 9, 13 are either stimulated or suppressed by Aur A or BRCA2, but the metastatic suppressors E-cadherin, β-catenin, and p53 are either inhibited or promoted by Aur A or BRCA2, leading to enhanced or reduced cell migration and invasion. Further study suggests that FBN1 inhibits E-cadherin and β-catenin, but stimulates MMP2, 9, 13. Depletion of SLUG abrogates FBN1 and MMP9, but increases E-cadherin, while p53 decreases both SLUG and FBN1. Animal assays demonstrate that FBN1 promotes both ovarian tumorigenesis and metastasis. Clinically, overexpression of BRCA2 or Aur A in ovarian cancer tissues predicts good or poor overall and disease free survivals. High expression of SLUG or FBN1 indicates poor overall survivals, whereas high expression of FBN1 but not of SLUG predicts poor disease free survival. No significant associations between p53 expression and patient survivals were found. Overall, FBN1, acts at the downstream of Aur A and BRCA2, promotes ovarian cancer metastasis through the p53 and SLUG-associated signaling, which may be useful for ovarian cancer diagnosis and treatment.

Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

“…Lentivirus carrying SIRT3 shRNA or STAT3 was generated and harvested as described previously. 34 Briefly, the cells were infected twice for a total of 4 days (2 days for each infection), and the positive clones were selected with puro23in (200 ng/mL) for 7-10 days. Control cell lines were generated by infection with viruses containing the empty vector following the same protocol.…”

Long non-coding RNA PGM5-AS1 modulates epithelial-mesenchymal transition and invasion and metastasis of osteosarcoma cells by impairing miR-140-5p-mediated FBN1 inhibition

“…Similarly, the depletion of lncRNA prostate cancer-associated transcript 1 has led to the repressed cell invasion, migration, proliferation, and EMT of osteosarcoma cells [35]. Also, ovarian cancer migration and invasion were revealed to be attenuated following FBN1 silencing [36]. Consistently, elevating the expression of miR-140…”

Long non‐coding RNA RP11‐552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer

“…41 As for ovarian cancers, BRCA2 inhibited ovarian cancer cell metastasis by regulating metastatic promoting markers (SLUG, FBN1, and MMP2, -9, -13), and overexpression of BRCA2 correlated with favorable DFS and OS in ovarian cancer patients. 42 Another study also showed that BRCA2 expression is associated with early-stage disease, low ascites incidence, younger age at diagnosis and low-grade tumors in endometrioid ovarian carcinoma patients. 43 This indicates the tumor suppressor role of BRCA2 in several cancers including ovarian cancer.…”