HMGA1 Interacts with β-Catenin to Positively Regulate Wnt/β-Catenin Signaling in Colorectal Cancer Cells
Tóm tắt
The high mobility group A1 (HMGA1) protein plays an important role in numerous biological processes, such as embryogenesis, cell proliferation, differentiation, apoptosis and carcinogenesis. Wnt/β-catenin signaling pathway plays a key role in development and cancer. Although previous reports have shown HMGA1 protein level can be induced by Wnt/β-catenin signaling pathway, however, the specific mechanism of HMGA1 on regulating Wnt/β-catenin signaling remains unclear. Here, we reported that HMGA1 interacted with β-catenin by using coimmunoprecipitation approach with exogenous and endogenous protein samples. HMGA1 positively regulated Wnt/β-catenin signaling, as determined by that HMGA1 increased the TOP-FLASH activity in a dose-dependent manner and β-catenin downstream target gene expression. Moreover, HMGA1 induced proliferation of colorectal cancer cells. Mechanistically, HMGA1 increased the β-catenin–TCF4 complex formation. Importantly, there was a correlation between HMGA1 and β-catenin expression in human colorectal cancer tissues. In summary, HMGA1 positively regulates Wnt/β-catenin signaling through interacting with β-catenin, which leads to increase the β-catenin–TCF4 complex formation. This suggests that targeting HMGA1 may be a useful therapeutic option in clinical application.
Tài liệu tham khảo
Fusco A, Fedele M (2007) Roles of HMGA proteins in cancer. Nat Rev Cancer 7:899–910
Shah SN, Kerr C, Cope L et al (2012) HMGA1 reprograms somatic cells into pluripotent stem cells by inducing stem cell transcriptional networks. PLoS One 7:e48533
Di Cello F, Shin J, Harbom K, Brayton C (2013) Knockdown of HMGA1 inhibits human breast cancer cell growth and metastasis in immunodeficient mice. Biochem Biophys Res Commun 434:70–74
Chiappetta G, Ottaiano A, Vuttariello E et al (2010) HMGA1 protein expression in familial breast carcinoma patients. Eur J Cancer 46:332–339
Takeuchi I, Takaha N, Nakamura T et al (2012) High mobility group protein AT-hook 1 (HMGA1) is associated with the development of androgen independence in prostate cancer cells. Prostate 72:1124–1132
Pang B, Fan H, Zhang IY et al (2012) HMGA1 expression in human gliomas and its correlation with tumor proliferation, invasion and angiogenesis. J Neurooncol 106:543–549
Hillion J, Smail SS, Di Cello F et al (2012) The HMGA1-COX-2 axis: a key molecular pathway and potential target in pancreatic adenocarcinoma. Pancreatology 12:372–379
Nezhad MH, Drieschner N, Helms S et al (2010) 6p21 rearrangements in uterine leiomyomas targeting HMGA1. Cancer Genet Cytogenet 203:247–252
Bush BM, Brock AT, Deng JA, Nelson RA Jr, Sumter TF (2013) The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer. Cell BiochemFunct 31:228–236
Zhang Y, Ma T, Yang S et al (2011) High-mobility group A1 proteins enhance the expression of the oncogenic miR-222 in lung cancer cells. Mol Cell Biochem 357:363–371
Clevers H, Nusse R (2012) Wnt/β-catenin signaling and disease. Cell 149:1192–1205
MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26
Rosenbluh J, Nijhawan D (2012) Cox AG: β-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell 151:1457–1473
Akaboshi S, Watanabe S, Hino Y et al (2009) HMGA1 is induced by Wnt/beta-catenin pathway and maintains cell proliferation in gastric cancer. Am J Pathol 175:1675–1685
Konsavage WM Jr, Kyler SL, Rennoll SA, Jin G, Yochum GS (2012) Wnt/β-catenin signaling regulates Yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J Biol Chem 287:11730–11739
Guo RJ, Funakoshi S, Lee HH, Kong J, Lynch JP (2010) The intestine-specific transcription factor Cdx2 inhibits beta-catenin/TCF transcriptional activity by disrupting the beta-catenin-TCF protein complex. Carcinogenesis 31:159–166
Emami KH, Nguyen C, Ma H et al (2004) A small molecule inhibitor of beta-catenin/CREB-binding protein transcription. Proc Natl Acad Sci U S A 101:12682–12687
Shah SN, Resar LM (2012) High mobility group A1 and cancer: potential biomarker and therapeutic target. Histol Histopathol 27:567–579
Giannini G, Cerignoli F, Mellone M, Massimi I, Ambrosi C, Rinaldi C, Gulino A (2005) Molecular mechanism of HMGA1 deregulation in human neuroblastoma. Cancer Lett 228:97–104