TSC-22 inhibits CSF-1R function and induces apoptosis in cervical cancer

• Published in: Oncotarget 2017-11, Vol.8 (58), p.97990-98003
• Main Authors: Cho, Min-Ji, Lee, Ji-Yeon, Shin, Min-Gwan, Kim, Hyun-Ji, Choi, Yu-Joung, Rho, Seung Bae, Kim, Boh-Ram, Jang, Ik Soon, Lee, Seung-Hoon
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.20296

Colony stimulating factor 1 receptor (CSF-1R) regulates the monocyte/macrophage system, which is an essential component of cancer development. Therefore, CSF-1R might be an effective target for anti-cancer therapy. The overexpression of transforming growth factor (TGF)-β stimulated clone-22 (TSC-22) inhibits cancer cell proliferation and induces apoptosis, and TSC-22 is emerging as a key factor in tumorigenesis. In this study, we discovered CSF-1R as a new interacting partner of TSC-22 and identified its elevated expression in cervical cancer cells. In particular, we found that TSC-22 interacted with the intracellular tyrosine kinase insert domain (539-749) of CSF-1R, which activates the AKT and ERK signaling pathways. This binding blocked AKT and ERK signaling, thereby suppressing the transcriptional activity of NF-κB. The overexpression of TSC-22 significantly decreased CSF-1R protein levels, affecting their autocrine loop. TSC-22 injected into a xenograft mouse model of human cervical cancer markedly inhibited tumor growth. The reduction of CSF-1R protein significantly suppresses cervical cancer cell proliferation and motility and induces apoptotic cell death. This association between TSC-22 and CSF-1R could be used as a novel therapeutic target and prognostic marker for cervical cancer.