Abstract
Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain stemness features, despite some controversies in age-related studies. GDF11 has been poorly investigated in cancer, particularly in those with stemness 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.
| Original language | English |
|---|---|
| Journal | Biochimica et Biophysica Acta - Molecular Basis of Disease |
| Volume | 1865 |
| Issue number | 6 |
| Pages (from-to) | 1540-1554 |
| Number of pages | 15 |
| ISSN | 0925-4439 |
| DOIs | |
| Publication status | Published - 01.06.2019 |
Funding
This work was partially funded by a grant from the Consejo Nacional de Ciencia y Tecnología (CONACYT; CB-252942 and Fronteras de la Ciencia-1320) and Universidad Autónoma Metropolitana . We thank the confocal core units of the Universidad Autonoma Metropolitana Iztapalapa, and Instituto Nacional de Cancerología de Mexico, for the assistance. MGR, SHR, ASN are scholarship holders from Conacyt. This work was partially funded by a grant from the Consejo Nacional de Ciencia y Tecnolog?a (CONACYT; CB-252942 and Fronteras de la Ciencia-1320) and Universidad Aut?noma Metropolitana. We thank the confocal core units of the Universidad Autonoma Metropolitana Iztapalapa, and Instituto Nacional de Cancerolog?a de Mexico, for the assistance. MGR, SHR, ASN are scholarship holders from Conacyt.
