Sp1 expression regulates lung tumor progression

Abstract

The role of specificity protein 1 (Sp1) in controlling gene expression in lung tumor development and metastasis is not well understood. In this study, we showed that the Sp1 level was highly increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycycline. Furthermore, the Sp1 level was highly upregulated in lung adenocarcinoma cells with low invasiveness and in patients with stage I lung cancer. We also demonstrated that Sp1 was downregulated in lung adenocarcinoma cells with high invasiveness and in patients with stage IV lung adenocarcinoma. Moreover, Sp1 inversely regulated migration, invasion and metastasis of lung adenocarcinoma cells in vivo. In addition, a decrease in the Sp1 level in highly invasive lung adenocarcinoma cells resulted from instability of the Sp1 protein. Furthermore, overexpression of Sp1 in highly invasive lung adenocarcinoma cells increased expression of E-cadherin, a suppressor of metastasis, and attenuated the translocation of β-catenin into the cellular nucleus that leads to tumor malignancy. Taken together, Sp1 level accumulated strongly in early stage and then declined in late stage, which is important for lung cancer cell proliferation and metastasis during tumorigenesis.

The Cyclin-dependent Kinase Inhibitor p16INK4a Physically Interacts with Transcription Factor Sp1 and Cyclin-dependent Kinase 4 to Transactivate MicroRNA-141 and MicroRNA-146b-5p Spontaneously and in Response to Ultraviolet Light-induced DNA Damage

“…Like p16, high expression of the Sp1 protein has been shown in many cancers and is highly correlated with the stage and poor prognosis (13,42). Furthermore, it has been recently shown that Sp1 level regulates lung tumor progression, and it strongly increases in the early stage and then decreases in the late stage, with high invasiveness of lung adenocarcinoma cells (43).…”

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

“…Indeed, the complex biological roles of SP1 might be context-dependent and regulated by interaction with cofactors (31). Hsu et al (17) reported that SP1 was negatively correlated with tumor progression in lung adenocarcinoma, but was required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors. The dual functions of SP1 in lung cancer are consistent with our proposed functions of FOXF2 in breast cancer.…”

“…has been implicated as a suppressor of human cancer progression (17). On the basis of a previous report on the role of FOXF2 in the suppression of metastasis in breast cancer, we speculated that FOXF2 mediates the SP1-suppressed aggressive phenotype in breast cancer cells.…”

Tumor-suppressing effects of microRNA-429 in human renal cell carcinoma via the downregulation of Sp1

“…Sp1 expression is tightly regulated throughout the various stages of tumorigenesis, which affects cancer progression (48). Previous studies concerning Sp1 expression in tumorigenesis suggest that increased transcription is the most important mechanism for Sp1 accumulation during cancer formation (49,50).…”