GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1865

Article

Gerardo-Ramirez, Monserrat^1,2  Lazzarini-Lechuga, Roberto³  Hernandez-Rizo, Shank^1,2  Esteban Jimenez-Salazar, Javier³  Simoni-Nieves, Arturo^1,2  Garcia-Ruiz, Carmen^4,5  Carlos Fernandez-Checa, Jose^4,5  Marquardt, Jens U.⁶  Coulouarn, Cedric⁷  Concepcion Gutierrez-Ruiz, Maria^2,8  Perez-Aguilar, Benjamin²  Gomez-Quiroz, Luis E.^2,8 

[1] Univ Autonoma Metropolitana Iztapalapa, DCBS, Posgrad Biol Expt, Mexico City, DF, Mexico

[2] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Av San Rafael Atlixco 186, Mexico City 09340, DF, Mexico

[3] Univ Autonoma Metropolitana Iztapalapa, Dept Biol Reprod, Mexico City, DF, Mexico

[4] CSIC, Inst Invest Biomed Barcelona, Dept Cell Death & Proliferat, Liver Unit,Hosp Clin,IDIBPAS, Barcelona, Spain

[5] CIBERehd, Barcelona, Spain

[6] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, Langenbeckstr 1, D-55131 Mainz, Germany

[7] Univ Rennes, INSERM, UMR 1241, INRA,Nutr Metab & Canc, Rennes, France

[8] UNAM Inst Nacl Cardiol Ignacio Chavez, Inst Invest Biomed, Unidad Med Translat, Lab Med Expt, Mexico City, DF, Mexico

关键词: GDF11;    Huh7 cells;    HCC;    Cell cycle;    Liver cancer;    Hep3B cells;   

DOI  :  10.1016/j.bbadis.2019.03.003

来源: Elsevier

【 摘 要 】

Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain sternness features, despite some controversies in age-related studies. GDF11 has been poorly investigated in cancer, particularly in those with sternness capacity, such as hepatocellular carcinoma (HCC), one of the most aggressive cancers worldwide. Here, we focused on investigating the effects of GDF11 in liver cancer cells. GDF11 treatment significantly reduced proliferation, colony and spheroid formation in HCC cell lines. Consistently, down-regulation of CDK6, cyclin D1, cyclin A, and concomitant upregulation of p27 was observed after 24 h of treatment. Interestingly, cell viability was unchanged, but cell functionality was compromised. These effects were potentially induced by the expression of E-cadherin and occludin, as well as Snail and N-cadherin repression, in a time-dependent manner. Furthermore, GDF11 treatment for 72 h induced that cells were incapable of sustaining colony and sphere capacity in the absent of GDF11, up to 5 days, indicating that the effect of GDF11 on self-renewal capacity is not transient. Finally, in vivo invasion studies revealed a significant decrease in cell migration of hepatocellular carcinoma cells treated with GDF11 associated to a decreased proliferation judged by Ki67 staining. Data show that exogenous GDF11 displays tumor suppressor properties in HCC cells.

【 授权许可】

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