Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma

Maly, Connor; Cumsky, Helen J.L.; Costello, Collin M.; Schmidt, Jessica; Butterfield, Richard J.; Zhang, Nan; DiCaudo, David J.; Nelson, Sara; Smith, Maxwell L.; Ochoa, Shari A.; Baum, Christian L.; Nagel, Thomas H.; Pittelkow, Mark R.; Sekulić, Aleksandar; Mangold, Aaron R.

doi:10.1016/j.jaad.2019.08.027

Cited by 16 publications

(12 citation statements)

References 19 publications

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“…Increasing loss of INPP5A expression has been observed in the progression of actinic keratoses to well‐differentiated cSCC to poorly‐differentiated metastatic cSCC, indicating its potential role in the development of carcinogenesis 3‐5 . Prior research has demonstrated the loss of INPP5A in high‐risk, recurrent, and metastatic cSCC and oropharyngeal squamous cell carcinoma 3‐5 . Our present study failed to corroborate these findings in a cohort of patients representative of the general population with cSCC, possibly due to the lack of poor outcomes in the overall cohort underpowering our dataset.…”

Section: Overall Population Invasive Tumors (Clark Level > I) Inpp5a Expression Level Total (N = 454) P Value Inpp5a Expression Level Totcontrasting

confidence: 71%

“…Inositol polyphosphate 5‐phosphatase A (INPP5A) is a cell membrane protein that negatively regulates inositol signaling and may be critical in cell signaling 2 . Our prior research demonstrated loss of INPP5A expression was significantly predictive of poor overall survival in high‐risk, recurrent, and metastatic cSCC 3 , 4 . The prognostic value of INPP5A in the general population with cSCC is unknown.…”

Section: Overall Population Invasive Tumors (Clark Level > I) Inpp5a Expression Level Total (N = 454) P Value Inpp5a Expression Level Totmentioning

confidence: 99%

Section: Overall Population Invasive Tumors (Clark Level > I) Inpp5a Expression Level Total (N = 454) P Value Inpp5a Expression Level Totmentioning

confidence: 99%

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The prognostic value of inositol polyphosphate 5‐phosphatase in cutaneous squamous cell carcinoma in the general population

et al. 2021

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Section: Overall Population Invasive Tumors (Clark Level > I) Inpp5a Expression Level Total (N = 454) P Value Inpp5a Expression Level Totcontrasting

confidence: 71%

Section: Overall Population Invasive Tumors (Clark Level > I) Inpp5a Expression Level Total (N = 454) P Value Inpp5a Expression Level Totmentioning

confidence: 99%

Section: Overall Population Invasive Tumors (Clark Level > I) Inpp5a Expression Level Total (N = 454) P Value Inpp5a Expression Level Totmentioning

confidence: 99%

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The prognostic value of inositol polyphosphate 5‐phosphatase in cutaneous squamous cell carcinoma in the general population

et al. 2021

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“…[53][54][55][56] Studies comparing specimens from various stages of progression (eg, in situ to invasive cSCC) have reported differential expression of various genes and microRNAs. 30,[57][58][59][60][61][62][63][64][65][66][67] However, few studies of prognostic biomarkers from primary tumors have been reported. 68,69 Many of the discriminant genes comprising the 40-GEP algorithm (Supplemental Table VI 70 ; available via Mendeley at https://doi.org/10.17632/f33w9wmng4.1) have been previously reported in cSCC and/or have known functions in cancer-relevant pathways.…”

Section: Discussionmentioning

confidence: 99%

Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

Wysong

Newman

Covington³

et al. 2021

Journal of the American Academy of Dermatology

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Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis.Objective: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management.Methods: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature

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“…Inositol polyphosphate 5-phosphatases are another kind of phosphatases, which are involved in regulating phosphorylation of phosphoinositide and associated with in a series of human pathologies such as the Lowe syndrome, the Joubert and MORM syndromes and several type of cancers [7][8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

INPP5F translocates into cytoplasm and interacts with ASPH to promote tumor growth in hepatocellular carcinoma

Zhou¹,

Lin²,

Liu³

et al. 2020

Preprint

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Background Increasing evidence has suggested inositol polyphosphate 5-phosphatase family contributes to tumorigenesis and tumor progression. However, the role of INPP5F in hepatocellular carcinoma (HCC) and its underlying mechanisms is unclear. Methods The expression of INPP5F in HCC was analyzed in public databases and our clinical specimens. The biological functions of INPP5F were investigated in vitro and vivo. The molecular mechanism of INPP5F in regulating tumor growth were studied by transcriptome-sequencing analysis, mass spectrometry analysis, immunoprecipitation assay and immunofluorescence assay. Results High expression of INPP5F was found in HCC tissues and was associated with poor prognosis in HCC patients. Overexpression of INPP5F promoted HCC cell proliferation, and vice versa. Knockdown of INPP5F suppressed tumor growth in vivo. Results from transcriptome-sequencing analysis showed INPP5F not only regulated a series of cell cycle related genes expression (c-MYC and cyclin E1), but also promoted many aerobic glycolysis related genes expression. Further study confirmed that INPP5F could enhance lactate production and glucose consumption in HCC cells. Mechanistically, INPP5F interacted with ASPH through which INPP5F activated Notch signaling and subsequently promoted the expression of c-MYC and cyclin E1. Interestingly, INPP5F was commonly nuclear-located in cells of adjacent tissues, while cytoplasmic-located was more common in HCC cells. LMB (nuclear export inhibitor) treatment restricted INPP5F in nucleus and was associated with inhibition of Notch signaling and cell proliferation. Furthermore, sequence of nuclear localization signals (NLSs) and nuclear export signals (NESs) in INPP5F aminoacidic sequence were identified. Alteration of the NLSs or NESs influenced the localization of INPP5F and the expression of its downstream molecules. Conclusion These findings indicate that INPP5F functions as an oncogene in HCC via a translocation mechanism and activating ASPH-mediated Notch signaling pathway. INPP5F may serve as a potential therapeutic target for HCC patients.

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Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma

Cited by 16 publications

References 19 publications

The prognostic value of inositol polyphosphate 5‐phosphatase in cutaneous squamous cell carcinoma in the general population

The prognostic value of inositol polyphosphate 5‐phosphatase in cutaneous squamous cell carcinoma in the general population

Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

INPP5F translocates into cytoplasm and interacts with ASPH to promote tumor growth in hepatocellular carcinoma

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