Spinophilin loss contributes to tumorigenesis in vivo

Ferrer, Irene; Peregrina, Sandra; Cañamero, Marta; Cecilia, Yolanda; Blanco‐Aparicio, Carmen; Carnero, Amancio

doi:10.4161/cc.10.12.15798

Cited by 13 publications

(16 citation statements)

References 25 publications

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“…However, in the absence of p53, reduced levels of Spn increase the tumorigenic properties of cells. In vivo, Spn knockout mice have a reduced lifespan, an increased number of tumors, and increased cellular proliferation (23). In addition, the combined loss of Spn and p53 activity leads to an increase in mammary carcinomas, confirming the functional relationship between p53 and Spn.…”

Section: Introductionmentioning

confidence: 57%

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Spinophilin Loss Correlates with Poor Patient Prognosis in Advanced Stages of Colon Carcinoma

Estévez-García

Lopez-Calderero

Molina-Pinelo

et al. 2013

Clinical Cancer Research

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Purpose: The genomic region 17q21 is frequently associated with microsatellite instability and LOH in cancer, including gastric and colorectal carcinomas. This region contains several putative tumor suppressor genes, including Brca1, NM23, prohibitin, and spinophilin (Spn, PPP1R9B, neurabin II). The scaffold protein Spn is one of the regulatory subunits of phosphatase-1 (PP1) that targets PP1 to distinct subcellular locations and couples PP1 to its target. Thus, Spn may alter cell-cycle progression via the regulation of the phosphorylation status of the retinoblastoma protein, a direct target of PP1. Therefore, we analyzed whether Spn levels were reduced in colorectal carcinomas and whether Spn levels correlated with prognosis or response to therapy.Experimental Design: By means of immunohistochemistry or quantitative PCR, we studied the levels of Spn in stages II, III, and IV colorectal carcinoma tumors and correlated to other clinicopathologic features as well as prognosis or response to therapy.Results: Spn was lost in a percentage of human gastric, small intestine, and colorectal carcinomas. In patients with colorectal carcinoma, tumoral Spn downregulation correlated with a more aggressive histologic phenotype (poorer tumor differentiation and higher proliferative Ki67 index). Consistent with this observation, lower Spn protein expression levels were associated with faster relapse and poorer survival in patients with stage III colorectal carcinoma, particularly among those receiving adjuvant fluoropyrimidine therapy. We validated this result in an independent cohort of patients with metastatic colorectal carcinoma treated with standard chemotherapy. Although patients that achieved an objective tumor response exhibited Spn levels similar to nontumoral tissue, nonresponding patients showed a significant reduction in Spn mRNA levels.Conclusions: Our data suggest that Spn downregulation contributes to a more aggressive biologic behavior, induces chemoresistance, and is associated with a poorer survival in patients with advanced stages of colorectal carcinoma.

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Section: Introductionmentioning

confidence: 57%

“…In this context, inactivation of p53 allows cells with lower levels of Spn to bypass senescence. This has been shown in mice (23) and in human lung tumors (15). We have data that this functional relationship between Spn loss and p53 mutations also exists in other tumors such as stomach tumors (data not shown).…”

Section: Discussionmentioning

confidence: 72%

Spinophilin Loss Correlates with Poor Patient Prognosis in Advanced Stages of Colon Carcinoma

Estévez-García

Lopez-Calderero

Molina-Pinelo

et al. 2013

Clinical Cancer Research

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“…36 Our data provide a functional explanation to several cancer studies that found a strong correlation between p53 mutations and the specific loss of the Spn locus (47.1% LOH).…”

Section: Methodsmentioning

confidence: 75%

“…The loss of Spn did not preclude the cells from entering senescence, and this response occurred with kinetics similar to WT cells. 36 However, Spn deficiency did affect the pattern of genetic alterations that occurred during MEF immortalization. Approximately 30% of the WT immortalized MEFs clones exhibited decreased p16 INK4 expression, and 50% of the clones carried p53 mutations.…”

confidence: 99%

Spinophilin acts as a tumor suppressor by regulating Rb phosphorylation

Ferrer¹,

Blanco‐Aparicio²,

Peregrina³

et al. 2011

Cell Cycle

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“…Rb hyperphosphorylée relâche E2F1, qui migre dans le noyau et induit la transcription des gènes dont les produits sont impliqués dans la transition G1S du cycle cellulaire. tumeur de la SPN dans des modèles in vivo en utilisant des souris modifiées génétiquement [8] [7]. La perte d'expression de la SPN est associée à un phénotype cellulaire moins différencié, un grade tumoral plus élevé et un mauvais pronostic.…”

Section: La Spinophiline Expression Tissulaire Et Partenairesunclassified

Levée de rideau sur la spinophiline, un suppresseur de tumeurs

Sarrouilhe

Ladevèze

2012

Med Sci (Paris)

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Spinophilin loss contributes to tumorigenesis in vivo

Cited by 13 publications

References 25 publications

Spinophilin Loss Correlates with Poor Patient Prognosis in Advanced Stages of Colon Carcinoma

Spinophilin Loss Correlates with Poor Patient Prognosis in Advanced Stages of Colon Carcinoma

Spinophilin acts as a tumor suppressor by regulating Rb phosphorylation

Levée de rideau sur la spinophiline, un suppresseur de tumeurs

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