Theranostics 2021; 11(7):3452-3471. doi:10.7150/thno.53572 This issue Cite

Research Paper

Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells

Eva M Verdugo-Sivianes1,2, Ana M Rojas3, Sandra Muñoz-Galván1,2, Daniel Otero-Albiol1,2, Amancio Carnero1,2✉

1. Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain.
2. CIBERONC, Instituto de Salud Carlos III, 28029 Madrid, Spain.
3. Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Universidad Pablo de Olavide, Sevilla, Spain.

Citation:
Verdugo-Sivianes EM, Rojas AM, Muñoz-Galván S, Otero-Albiol D, Carnero A. Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells. Theranostics 2021; 11(7):3452-3471. doi:10.7150/thno.53572. https://www.thno.org/v11p3452.htm
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Abstract

Graphic abstract

Rationale: SPINOPHILIN (SPN, PPP1R9B) is an important tumor suppressor involved in the progression and malignancy of different tumors depending on its association with protein phosphatase 1 (PP1) and the ability of the PP1-SPN holoenzyme to dephosphorylate retinoblastoma (pRB).

Methods: We performed a mutational analysis of SPN in human tumors, focusing on the region of interaction with PP1 and pRB. We explored the effect of the SPN-A566V mutation in an immortalized non-tumorigenic cell line of epithelial breast tissue, MCF10A, and in two different p53-mutated breast cancer cells lines, T47D and MDA-MB-468.

Results: We characterized an oncogenic mutation of SPN found in human tumor samples, SPN-A566V, that affects both the SPN-PP1 interaction and its phosphatase activity. The SPN-A566V mutation does not affect the interaction of the PP1-SPN holoenzyme with pocket proteins pRB, p107 and p130, but it affects its ability to dephosphorylate them during G0/G1 and G1, indicating that the PP1-SPN holoenzyme regulates cell cycle progression. SPN-A566V also promoted stemness, establishing a connection between the cell cycle and stem cell biology via pocket proteins and PP1-SPN regulation. However, only cells with both SPN-A566V and mutant p53 have increased tumorigenic and stemness properties.

Conclusions: SPN-A566V, or other equivalent mutations, could be late events that promote tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the tumor.

Keywords: SPINOPHILIN, PP1, cancer stem cell, tumorigenesis, stem cell phenotype, pRB, pocket proteins


Citation styles

APA
Verdugo-Sivianes, E.M., Rojas, A.M., Muñoz-Galván, S., Otero-Albiol, D., Carnero, A. (2021). Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells. Theranostics, 11(7), 3452-3471. https://doi.org/10.7150/thno.53572.

ACS
Verdugo-Sivianes, E.M.; Rojas, A.M.; Muñoz-Galván, S.; Otero-Albiol, D.; Carnero, A. Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells. Theranostics 2021, 11 (7), 3452-3471. DOI: 10.7150/thno.53572.

NLM
Verdugo-Sivianes EM, Rojas AM, Muñoz-Galván S, Otero-Albiol D, Carnero A. Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells. Theranostics 2021; 11(7):3452-3471. doi:10.7150/thno.53572. https://www.thno.org/v11p3452.htm

CSE
Verdugo-Sivianes EM, Rojas AM, Muñoz-Galván S, Otero-Albiol D, Carnero A. 2021. Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells. Theranostics. 11(7):3452-3471.

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