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GDF11 knockdown downregulates SMURF1 to inhibit breast cancer progression by activation of p53 and inactivation of ERα signaling.
Tang, Hai-Li; Wang, Qi; Lu, Jian-Guo; Yang, Xiao-Jun; Shi, Jiao-Jiao; Wang, Sheng-Peng; Cao, Chang-Qing; Zhao, Hua-Dong.
Affiliation
  • Tang HL; Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
  • Wang Q; Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
  • Lu JG; Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
  • Yang XJ; Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
  • Shi JJ; Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
  • Wang SP; Department of Urinary Surgery, The 4th People's Hospital of Qinghai Province, Xining, Qinghai, China.
  • Cao CQ; Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
  • Zhao HD; Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
Neoplasma ; 69(6): 1386-1395, 2022 Dec.
Article in En | MEDLINE | ID: mdl-36591801
ABSTRACT
Breast cancer (BC) is a prevalent neoplasm that occurs in women all over the world. Growth and differentiation factor 11 (GDF11) plays an essential role in cancer progression. This study focused on investigating the biological role and underlying mechanisms of GDF11 in BC. We detected the expression of GDF11 in 27 patients with BC and BC cell lines. Kaplan-Meier plotter was employed to analyze the relationship between GDF11 expression and overall survival (OS) of BC patients. The proliferative, migratory, invasive, and apoptotic abilities of T47D cells were examined. Correlation analysis of GDF11 with Smad ubiquitination regulatory factor 1 (SMURF1) was conducted. The association between GDF11 and the p53 pathway was analyzed by western blot and PFT-α (a p53 inhibitor)-mediated rescue assays. A brief analysis of the role of estrogen receptor alpha (ERα) signaling in BC progression was performed. The results showed that GDF11 was increased in BC tissues and cell lines, and the high expression of GDF11 was associated with the poor OS of BC patients. GDF11 knockdown inhibited the proliferation, migration, and invasion of T47D cells, but promoted cell apoptosis. Meanwhile, the GDF11 knockdown reduced the SMURF1 expression and invoked the p53 pathway activation. SMURF1 overexpression and PFT-α partially blocked the effects of GDF11 knockdown. In addition, GDF11 knockdown and SMURF1 silencing inhibited the activation of the ERα signaling pathway. In summary, GDF11 was involved in the progression of BC by regulating SMURF1-mediated p53 and ERα pathways, opening up a new way for BC treatment.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms Limits: Female / Humans Language: En Journal: Neoplasma Year: 2022 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms Limits: Female / Humans Language: En Journal: Neoplasma Year: 2022 Type: Article Affiliation country: China