Activin receptor signaling regulates prostatic epithelial cell adhesion and viability

Area of Science:

• Oncology
• Cell Biology
• Molecular Signaling

Background:

• Carcinogenesis involves cell division regulated by various signals, but specific hormone signals remain unclear.
• Fetal serum is essential for in vitro cell proliferation, indicating the presence of critical growth factors.

Purpose of the Study:

• To identify fetal serum components and signaling pathways essential for prostate cancer cell proliferation (PCC).
• To investigate the role of activin A and its receptor, activin receptor type II (ActRII), in PCC viability and metastasis.

Main Methods:

• Utilized prostatic cancer cell (PCC) lines as a model system.
• Investigated the effects of activin A, inhibin A, basic fibroblast growth factor, and ActRII signaling inhibitors (blocking antibody, antisense-P).
• Assessed Smad2 phosphorylation, cell viability, apoptosis (caspase 3 activity), cell adhesion, and ADAM-15 expression.

Main Results:

• Activin A signaling through ActRII is necessary, though not sufficient, for PCC proliferation in the presence of fetal bovine serum (FBS).
• Inhibition of ActRII signaling decreased PCC and neuroblastoma cell viability and Smad2 phosphorylation but did not induce apoptosis.
• Suppression of ActRII signaling correlated with increased cell detachment and ADAM-15 expression, a marker of prostate cancer metastasis.

Conclusions:

• ActRII signaling is essential for the viability of PCC and neuroblastoma cells, regulating cell fate through cell adhesion mechanisms.
• The findings highlight ActRII's dual role in cell viability and adhesion, suggesting its potential as a therapeutic target for managing cancer growth and metastasis.