Depletion of SENP1 suppresses the proliferation and invasion of triple-negative breast cancer cells

Abstract

To investigate the roles of SUMO-specific protease 1 (SENP1) in triple-negative breast cancer (TNBC), we detected the expression level of SENP1 in the clinical samples of TNBC and non‑TNBC patients by using immunohistochemical staining, qRT‑PCR, and western blotting. We found that SENP1 was highly expressed in the TNBC tissues compared with the normal breast tissues, as well as non‑TNBC tissues. Next, we constructed the si‑SENP1‑transfected TNBC cell lines for further biological function investigation. Then a xenograft model of nude mice was constructed to confirm the roles of SENP1 in TNBC formation and metastasis. According to our results, deficiency of SENP1 significantly represses the proliferation, invasion, migration, and colony formation of TNBC cells through blocking the cell cycle and regulating the expression of cyclin‑dependent kinases (CDKs) p21 and p27, as well as MMP9. Furthermore, in vivo experiments revealed that depletion of SENP1 remarkably inhibits the tumor volume, lung metastatis and the expression of p21, p27, MMP9, and Ki67. Taken together, this study elucidated that SENP1 is essential for TNBC cell proliferation and migration in vitro, as well as tumor formation and metastasis in vivo, indicating that SENP1 is a potential therapeutic target for TNBC treatment.

The post-translational modification, SUMOylation, and cancer (Review)

“…Hypoxia (low oxygen supply) aids tumor metastasis, in part by promoting EMT in cancer cells. SENP1 has been shown to enhance the invasion and lung metastasis of triple-negative breast cancer (TNBC) cells in a xenograft tumor model with nude mice ( 163 ). SENP1 promotes prostate cancer progression and bone metastasis by regulating two bone remodeling proteins, matrix metalloproteinase (MMP)-2 and MMP-9, through the HIF1α signaling pathway ( 164 ).…”

SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation

“…SUMOylation is a dynamic process, and can be reversed by SUMO-specific cysteine proteases (SENPs). One such protease SENP1 has been widely investigated in many cancers including prostate cancer, breast cancer and colon cancer [3,4]. Prostate cancer is the most commonly diagnosed cancer in United States and is also on rapid rise in China [5].…”

SENP1 is required for the growth, migration, and survival of human adipose-derived stem cells

“…It was similarly reported that the Inhibition of SENP1 in neuroblastoma cells significantly suppressed their migration and invasion capacity [29]. SENP1 silencing also attenuated the growth and invasiveness of triplenegative breast cancer cells [30]. The culmination of these studies implicates SENP1 in the numerous important physiological and basic functions of cells.…”