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SATB1 Promotes Pancreatic Cancer Growth and Invasion Depending on MYC Activation.

ABSTRACT: SATB1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SATB1 promotes pancreatic cancer tumorigenesis.To investigate SATB1 expression levels and its biological functions in promoting pancreatic cancer growth and invasion.SATB1 expression levels were detected in seven human pancreatic cancer cell lines and 16 pairs of normal pancreatic/pancreatic cancer tissues using RT-PCR and western blot. SW1990 or Capan-1 cells stably knockdown (shRNA) or transiently knockdown (siRNA) SATB1 cells, and PANC-1 stably overexpressing SATB1 cells were investigated with MTT, EdU assay, flow cytometry, and transwell invasion assay for cell proliferation and invasion activity. The binding of SATB1 to MYC promoter region was examined using reporter assay. Expression of SATB1 in 68 pancreatic cancer samples was studied by immunohistochemical staining and scoring.SATB1 was overexpressed in pancreatic cancer tissues samples, showing strong correlation with pancreatic cancer invasion depth and tumor staging. SATB1 induced MYC mRNA and protein expression; promoted pancreatic cancer cell growth; increased cell population in S phase; and enhanced pancreatic cancer cell invasion in vitro. On the other hand, SATB1 knockdown showed opposite effects. Furthermore, MYC blocking in SATB1-overexpressing cells attenuated the promotion of pancreatic cancer cell growth and invasion. Our data also indicated that SATB1 bound to specific promoter region of MYC.SATB1 is overexpressed in pancreatic cancer, promoting cancer cell proliferation and invasion through the activation of MYC.

SUBMITTER: Chen Z

PROVIDER: S-EPMC4621700 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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SATB1 Promotes Pancreatic Cancer Growth and Invasion Depending on MYC Activation.

Chen Zheng Z Li Zengliang Z Li Wei W Zong Yang Y Zhu Yi Y Miao Yi Y Xu Zekuan Z

Digestive diseases and sciences 20150625 11

<h4>Background</h4>SATB1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SATB1 promotes pancreatic cancer tumorigenesis.<h4>Aims</h4>To investigate SATB1 expression levels and its biological functions in promoting pancreatic cancer growth and invasion.<h4>Methods</h4>SATB1 expression levels were detected in seven human pancreatic c ...[more]

PMID: 26108419

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Project description:Special AT-rich sequence-binding protein-1 (SATB1) has been identified as a genome organizer that reprograms chromatin organization and transcription profiles. SATB1 promotes tumor growth and metastasis in breast cancer and is associated with poor prognosis in several cancer types. The association between SATB1 and colorectal cancer (CRC) has not been studied intensively. Therefore, this study aimed to investigate the effect of SATB1 on CRC growth and metastasis in vitro and in vivo and its correlation with overall survival and clinicopathological factors in CRC patients. Stable SATB1 knockdown and SATB1-overexpressing cell lines were established. SATB1 knockdown decreased cell growth, colony formation, migration, and invasion and increased apoptosis in CRC cells in vitro (p<0.05), whereas SATB1 overexpression had the opposite effect. SATB1 overexpression increased tumor growth and metastasis to lung and liver in vivo by using xenograft animal models (p<0.05). Thus, SATB1 promoted an aggressive CRC phenotype in vitro and in vivo. Immunohistochemical analysis of 560 CRC specimens showed that SATB1 expression was significantly higher in CRC tissues than in matched non-tumor mucosa (p<0.001). In addition, SATB1 expression was significantly higher in patients with poorly differentiated tumors, higher invasion depth, distant metastasis, and advanced TNM stage. SATB1-positive patients had a poorer prognosis than SATB1-negative patients, and SATB1 was identified as an independent prognostic factor for CRC (p = 0.009). Strikingly, we also evaluated SATB2 expression in CRC and found that SATB2 was more abundantly expressed in non-cancerous mucosa compared to colorectal cancer tissues (p<0.001). However, SATB2 expression had no influence on prognosis of CRC patients (p = 0.836). SATB1 expression was significantly associated with shorter survival time either in SATB2-positive patients or in SATB2-negative patients (p<0.001). In conclusion, our findings indicated an important role for SATB1 in CRC tumorigenesis and metastasis. Therefore, SATB1 may represent an important prognostic biomarker and therapeutic target for CRC.

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SATB1 Promotes Pancreatic Cancer Growth and Invasion Depending on MYC Activation.

Publications

SATB1 Promotes Pancreatic Cancer Growth and Invasion Depending on MYC Activation.

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