Activin B induces human endometrial cancer cell adhesion, migration and invasion by up-regulating integrin β3 via SMAD2/3 signaling.

Abstract

Endometrial cancer is the fourth most common female cancer and the most common gynecological malignancy. Although it comprises only ~10% of all endometrial cancers, the serous histological subtype accounts for ~40% of deaths due to its aggressive behavior and propensity to metastasize. Histopathological studies suggest that elevated expression of activin/inhibin βB subunit is associated with reduced survival in non-endometrioid endometrial cancers (type II, mostly serous). However, little is known about the specific roles and mechanisms of activin B (βB dimer) in serous endometrial cancer growth and progression. In the present study, we examined the biological functions of activin B in type II endometrial cancer cell lines, HEC-1B and KLE. Our results demonstrate that treatment with activin B increases cell migration, invasion and adhesion to vitronectin, but does not affect cell viability. Moreover, we show that activin B treatment increases integrin β3 mRNA and protein levels via SMAD2/3-SMAD4 signaling. Importantly, siRNA knockdown studies revealed that integrin β3 is required for basal and activin B-induced cell migration, invasion and adhesion. Our results suggest that activin B-SMAD2/3-integrin β3 signaling could contribute to poor patient survival by promoting the invasion and/or metastasis of type II endometrial cancers.

• Authors: Siyuan Xiong, Christian Klausen, Jung-Chien Cheng, Hua Zhu, Peter C K Leung
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 31 Pg. 31659-73 (Oct 13 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26384307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• INHBB protein, human
• Integrin beta3
• RNA, Messenger
• RNA, Small Interfering
• SMAD2 protein, human
• SMAD3 protein, human
• Smad2 Protein
• Smad3 Protein
• Inhibin-beta Subunits

Topics

• Apoptosis
• Blotting, Western
• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Endometrial Neoplasms (drug therapy, genetics, metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Inhibin-beta Subunits (pharmacology)
• Integrin beta3 (chemistry, genetics, metabolism)
• Neoplasm Invasiveness
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Smad2 Protein (antagonists & inhibitors, genetics, metabolism)
• Smad3 Protein (antagonists & inhibitors, genetics, metabolism)
• Tumor Cells, Cultured