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Analysis of Potential Alterations Affecting SETBP1 as a Novel Contributing Mechanism to Inhibit PP2A in Colorectal Cancer Patients

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Abstract

Background

The functional loss of the tumor suppressor protein phosphatase 2A (PP2A) occurs in a wide variety of human cancers including colorectal cancer (CRC), and SET overexpression has been reported as a key contributing mechanism to inhibit PP2A. Although SET binding protein 1 (SETBP1) overexpression and gain of function mutations have been described in several hematological malignancies as common events that increase the expression levels of the PP2A inhibitor SET, thereby leading to PP2A inactivation, the potential existence of SETBP1 alterations in CRC still remains unexplored.

Methods

We studied the expression profile of SETBP1 by Western blot in a set of CRC cell lines and patient samples. Moreover, we performed co-immunoprecipitation assays to analyze the formation of the previously reported SETBP1–SET–PP2A inhibitory complex. Furthermore, we evaluated the mutational status of SETBP1 by pyrosequencing assays in a cohort of 55 CRC patients with metastatic disease after the immunohistochemical characterization of SET and p-PP2A expression in this cohort.

Results

We found high SETBP1 expression in several CRC lines but only in two of the patients analyzed. In addition, we demonstrated the formation of the SETBP1–SET–PP2A heterotrimeric complex in CRC cells. However, we failed to detect SETBP1 mutations in any of the CRC patient samples included in the study.

Conclusions

Our results suggest that SETBP1 expression is mainly similar o lower in colorectal cancer tissue compared to normal colonic mucosa. However, its overexpression is a low prevalent alteration which could contribute to inhibit PP2A in CRC through the formation of a SETBP1–SET–PP2A complex in some CRC patients. Moreover, SETBP1 mutations are, if exist, rare events in CRC patients.

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Acknowledgments

This work was supported by PI15/00934 and PI16/01468 grants from “Instituto de Salud Carlos III FEDER”, Spain. B.T. is supported by “Fundación Conchita Rábago de Jiménez Díaz”.

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Authors and Affiliations

  1. Translational Oncology Division, Oncohealth Institute, IIS-Fundación Jiménez Diaz, Autonomous University of Madrid, University Hospital “Fundación Jiménez Diaz”, Avda. Reyes Católicos-2, 28040, Madrid, Spain

    Blanca Torrejón, Ion Cristóbal, Cristina Caramés, Cristina Chamizo, Andrea Santos, Roberto Serna-Blasco & Jesús García-Foncillas

  2. Pathology Department, Autonomous University of Madrid, University Hospital “Fundación Jiménez Diaz”, 28040, Madrid, Spain

    Iván Prieto-Potín, Marta Sanz-Alvarez, Melania Luque, Juan Madoz-Gúrpide & Federico Rojo

Authors
  1. Blanca Torrejón
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  2. Ion Cristóbal
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  3. Cristina Caramés
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  4. Iván Prieto-Potín
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  12. Jesús García-Foncillas
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Corresponding authors

Correspondence to Ion Cristóbal or Jesús García-Foncillas.

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Torrejón, B., Cristóbal, I., Caramés, C. et al. Analysis of Potential Alterations Affecting SETBP1 as a Novel Contributing Mechanism to Inhibit PP2A in Colorectal Cancer Patients. World J Surg 42, 3771–3778 (2018). https://doi.org/10.1007/s00268-018-4684-9

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  • DOI: https://doi.org/10.1007/s00268-018-4684-9

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