SATB1 mediated tumor colonization and β-catenin nuclear localization are associated with colorectal cancer progression

ABSTRACT

Colorectal cancer (CRC) is a malignancy with high incidence and poor prognosis. It is urgent to identify valuable biomarkers for early diagnosis and potent therapeutic targets. It has been reported that SATB1 is associated with the malignant progression in CRC. To explore the role of SATB1 in CRC progression and the underlying mechanism, we evaluated the expression of SATB1 in the paired CRC tissues with immunohistochemistry. The results showed that the expression of SATB1 in lymph node metastasis was higher than that in primary lesion, and that in distant organ metastasis was higher than that in primary lesion. The retrospective analysis showed that patients with high expression of SATB1 had a significantly worse prognosis than those with negative and moderate expression. In vitro experiments that employing SATB1 over-expressing and depleted CRC cell lines confirmed that SATB1 contributes to cell proliferation and colonization, while inhibiting cell motility. Furthermore, the tissue immunofluorescence assay, Co-IP and Western blot were conducted to reveal that SATB1 induced translocation of β-catenin and formed a protein complex with it in the nuclei. In conclusion, SATB1 mediated tumor colonization and β-catenin nuclear localization are associated with the malignant progression and poor prognosis of CRC.

KEYWORDS:

• Colorectal cancer progression
• SATB1
• tumor colonization
• β-catenin

Disclosure statement

No potential conflict of interest was reported by the authors.

Authors’ contributions

L.S. and J.H.L. designed the study and analyzed the data. F.W. contributed to histology review. X.F.W. and F.Y.Z. performed the in vitro experiment. S.J.M. collected the data. All authors read and approved the final manuscript.

Ethical approval and consent to participate

This publication is approved by the Ethics Committee of the Affiliated Suzhou Hospital of Nanjing Medical University (K-2022-018-K01). The participants in the study gave verbal regarding.

Data availability statement

The datasets used and analyzed in the present study are available from the corresponding author upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384047.2024.2320307

Additional information

Funding

This work was supported by the funds of the Gusu Health Talents Project [GSWS2019054]; the Suzhou Science and Technology Development Plan [SKJYD2021107].

Notes on contributors

Luan Sun

Luan Sun received her B.S. and Ph.D. degree from Nanjing Medical University in 2006, and 2011. Currently, she is an associate professor in the Department of Cell Biology at Nanjing Medical University College of Basic Medical Sciences. Her research focuses on T-cell biology and CAR-T cell therapy.

Feng Wang

Feng Wang received her B.S. and M.S. degree in School of Medicine from Soochow University in 2004 and 2014. Now she is an associate chief physician in the Department of Pathology of Suzhou Municipal Hospital. Her research focuses on pathological diagnosis of digestive tract tumors.

Xufei Wang

Xufei Wang studies a Master’s degree in Cell Biology at Nanjing Medical University. His research focuses on the mechanisms of CAR-T cell exhaustion.

Feiying Zhang

Feiying Zhang studies a Bachelor degree in Clinical Medicine Science at Nanjing Medical University.

Sujuan Ma

Sujuan Ma received her B.S. degree from Liaocheng University in 2008 and M.S. degree from Xiamen University. She is currently working in the Department of Cell Biology at Nanjing Medical University College of Basic Medical Sciences.

Jinghuan Lv

Jinghuan Lv received her B.S. and M.S. degree from Nanjing Medical University in 2003 and 2009. She received her Ph.D. degree in Pathology from Nanjing University in 2017. Now she is an associate professor of Nanjing Medical University, and director of the Department of Pathology at Suzhou Municipal Hospital. Her research focuses on the diagnosis and pathogenesis of gastrointestinal tumors.