C-terminal binding protein-2 promotes cell proliferation and migration in breast cancer via suppression of p16INK4A

Abstract

C-terminal binding protein-2 (CtBP2) enhances cancer proliferation and metastasis. The role and mechanism of CtBP2 in breast cancer remains to be elucidated. Western blot and immunochemistry were employed to evaluate the level of CtBP2 and p16INK4A in breast cancer. Genetic manipulation was used to study the expression of p16INK4A and its downstream genes regulated by CtBP2. Functional assays, including colony formation, wound healing, transwell invasion, anchorage-independent growth assay and a xenograft tumor model were used to determine the oncogenic role of CtBP2 in breast cancer progression. The expression of CtBP2 was increased in breast cancer tissues and cell lines. The expression of p16INK4A were inversely correlated CtBP2 (r2 = 0.43, P < 0.01). The expression of both CtBP2 and p16INK4A were significantly related to histological differentiation (P < 0.01 and P = 0.004, respectively) and metastasis (P = 0.046 and 0.047, respectively). The overall survival rate was lower in patients with increased CtBP2 expression and lower p16INK4A expression. Knockdown of CtBP2 resulted in the activation of p16INK4A and down–regulation of cell cycle regulators cyclin D, cyclin E and cyclin-dependent kinase 2 and 4. This down-regulation also led to a decreased transition of the G1-S phase in breast cancer cells. Moreover, gain-of-function experiments showed that CtBP2 suppressed p16INK4A and matrix metalloproteinase-2, subsequently enhancing the migration in breast cancer. However, the silence of CtBP2 abrogated this effect. Collectively, these findings provide insight into the role CtBP2 plays in promoting proliferation and migration in breast cancer by the inhibition of p16INK4A.

Effects of gametogenetin‐binding protein 2 on proliferation, invasion and migration of prostate cancer PC‐3 cells

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C-terminal binding protein‑2 mediates cisplatin chemoresistance in esophageal cancer cells via the inhibition of apoptosis

“…It has been reported that CtBP2 has a critical function in tumorigenesis and tumor progression (20,21). CtBP2 is overexpressed in a number of different tumor types, including hepatocellular carcinoma (22), prostate cancer (23), breast cancer (24,25) and ovarian cancer (26). Furthermore, preliminary studies conducted by the present research team revealed that the…”

ZBTB18 inhibits SREBP-dependent fatty acid synthesis by counteracting CTBPs and KDM1A/LSD1 activity in glioblastoma

“…1B). CTBPs are co-repressors which are implicated in human cancer by promoting several pro-oncogenic activities including EMT, cell survival, migration and invasion (28)(29)(30). We validated the interactions by co-immunoprecipitation in multiple experiments using different antibodies directed to ZBTB18 or CTBP2 (Fig.…”