Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis

Pandey, Poomy; Rachagani, Satyanarayana; Das, Srustidhar; Sheinin, Yuri; Naslavsky, Naava; Pan, Zenggang; Smith, Brittney L.; Peters, Haley L.; Radhakrishnan, Prakash; McKenna, Nicole R.; Giridharan, Sai Srinivas Panapakkam; Haridas, Dhanya; Kaur, Sukhwinder; Hollingsworth, Michael A.; MacDonald, Richard G.; Meza, Jane L.; Caplan, Steve; Batra, Surinder K.; Solheim, Joyce C.

doi:10.18632/oncotarget.2990

Cited by 27 publications

(46 citation statements)

References 22 publications

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“…At present, the signalling pathways by which APLP2 wields its effects in cancer cells are poorly understood. Pandey et al (5) determined that loss of APLP2 decreased cortical actin and increased intracellular actin filaments in pancreatic cancer cells, reducing the ability of these cells to migrate and invade. Other studies demonstrated that APLP2 can regulate major histocompatibility complex class I molecule expression in cancer cells and increase cancer immune evasion (17,18).…”

Section: Discussionmentioning

confidence: 99%

“…The human APLP2 gene is located at 11q24 and is expressed in the majority of tissues (4). It has been demonstrated that APLP2 expression is involved in the development of a number of cancer types, including pancreatic, colon, breast and prostate cancer (5). APLP2 has been associated with certain characteristics of cancer cells, including abnormal growth, migration and invasion, which indicates that APLP2 may significantly affect the development and progression of cancer (6); however, the expression and function of APLP2 in RCC remains undefined.…”

Section: Introductionmentioning

confidence: 99%

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Role of APLP2 in the prognosis and clinicopathology of renal cell carcinoma

et al. 2018

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Identifying diagnostic and prognostic biomarkers is crucial for improved guidance of the treatment of renal cell carcinoma (RCC). Amyloid β precursor-like protein 2 (APLP2) has been determined to serve an important role in the progression of a number of cancer types. However, the expression and significance of APLP2 in RCC remains unknown. In the present study, it was determined that the expression of APLP2 protein (n=10) and mRNA (n=8) expression was significantly decreased in clear cell RCC (CCRCC) tissues compared with that in matched normal renal tissues. The expression level of APLP2 was significantly associated with high Fuhrman grade, high pT stage, and presence of distant metastasis and lymph node metastasis (P<0.05). Multivariate analysis demonstrated that the expression of APLP2 was a significant independent predictor of disease-specific survival in renal cell carcinoma (P=0.026). Notably, APLP2 expression was significantly associated with disease-specific survival (P<0.001). APLP2 may be used to potentially predict patient prognosis, and to guide clinical diagnosis and treatment in CCRCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of APLP2 in the prognosis and clinicopathology of renal cell carcinoma

et al. 2018

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“…As reported previously, APLP2 has biochemical functions related to cell migration, signaling, adhesion, proliferation, and healing [9,13,17,32]. Recently, dysregulation of APLP2 has been found in multiple cancer types, such as colorectal cancer, lung cancer, breast cancer, pancreatic cancer, and Ewing's sarcoma, and to be involved in abnormal growth, invasion, and metastasis [1,2,16,21,24,29]. However, the expression pattern (increase or decrease) of APLP2 is found inconsistent from cancer to cancer, though the consequences are not really clear [22].…”

Section: Introductionmentioning

confidence: 89%

Expression of amyloid precursor-like protein 2 (APLP2) in glioblastoma is associated with patient prognosis

Chen¹,

Wang²,

Tan³

et al. 2018

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The purpose of this study was to investigate the expression status of amyloid precursor-like protein 2 (APLP2) and its clinical relevance in patients with glioblastoma. The publically available database Project Betastasis involving Repository for Molecular Brain Neoplasia Data (REMBRANDT) and The Cancer Genome Atlas (TCGA) was first utilized to analyze the expression and prognostic potential of APLP2 in glioblastoma. Compared with normal controls, the glioblastoma group from each dataset showed no significant difference of APLP2 expression (p > 0.05). However, when connected to glioblastoma patient's prognosis, a high APLP2 expression was found to be associated with short overall survival in REMBRANDT cases (p = 0.0323) but not the TCGA group (p = 0.0578). Consistently, APLP2 expression detected by immunohistochemistry in our cohort revealed an undifferentiated expression pattern between glioblastoma (n = 114) and normal brain (n = 16) (p = 0.265) and among all grade gliomas. Furthermore, univariate and multivariate analyses identified a high APLP2 expression as an independent risk factor for overall survival (hazard ratio = 1.537, p = 0.041) and progression-free survival (hazard ratio = 1.783, p = 0.037) of glioblastoma patients. In conclusion, the expression of APLP2 might correlate with tumor development and be a prognostic factor for patients with glioblastoma.

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“…Full automation was provided by custom software that allows parallel event coordination and therefore near 100% MS duty cycle through use of two trapping and analytical columns. RP columns were slurry packed in-house with 3 m Jupiter C 18 (Phenomenex, Torrence, CA) into fused silica columns that were 40 Data acquisition lagged the gradient start and end times by 15 min to account for column dead volume allowing for the highest throughput when running in two-column operation mode, so that the columns could to be washed (shortened gradients) and re-generated off-line without any cost to the duty cycle.…”

Section: Experimental Design and Statistical Rational: Lc-ms And Lc-imentioning

confidence: 99%

“…Of significant interest was the detection of MEPCE, FAP and APLP2, which in addition to ranking high in at least 50% of HPA breast cancer stains, have been positively correlated with invasive and metastatic potential. RNA methyltransferase (MEPCE -7SK snRNA methylphosphate capping enzyme) has been found to be overexpressed in highly tumorigenic breast cancer stem cells (36,37), prolyl endopeptidase FAP (FAP) is a cell surface glycoprotein serine protease that participates in malignant cell invasiveness by degrading the extracellular matrix (38) and amyloid-like protein 2 (APLP2) has higher expression within invasive breast cancer because it promotes rearrangement of the actin cytoskeleton by increasing cortical actin (39,40). Detection of these proteins illustrates the power of DTM analyses for finding new information in a high throughput unfractionated approach while simultaneously targeting specific proteins.…”

Section: Dtm With Lc-ims-ms Compared With Lc-ms and Lc-ms/msmentioning

confidence: 99%

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry

Nie

Casey

Monroe

et al. 2016

Molecular & Cellular Proteomics

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Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. The application of both discovery and targeted proteomics approaches is increasingly important across many areas of biological research, such as elucidating molecular mechanism of disease progression and increasing the utility of clinical applications to facilitate early detection and prognostic classification (1, 2). Currently discovery and targeted approaches are performed separately, limiting sample throughput and requiring more material for thorough analyses. In the prevalent discovery-based shotgun approach (3-6), proteins are digested into peptides, separated by liquid chromatography (LC) 1 , and detected by mass spectrometry (MS), where specific peptides are further selected (typically by abundance) for successive tandem MS/MS for identification. The resulting spectra are then mapped to peptide or protein sequences using highly-evolved database search algorithms with results normally obtained for thousands of unique proteins. However, the large numbers of coeluting peptides and use of MS/MS inevitably limit proteomic measurement effectiveness by at least one of three key metrics: throughput, sensitivity, and proteome coverage. To increase proteome coverage additional fractionation steps and/or extended LC separations are often applied. Although this is advantageous for increasing the comprehensiveness and sensitivity of measurements, the reduced throughput greatly restricts the ability to account for both measurement and biological variability. Additionally, these broad discovery measurements still suffer deficiencies

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Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis

Cited by 27 publications

References 22 publications

Role of APLP2 in the prognosis and clinicopathology of renal cell carcinoma

Role of APLP2 in the prognosis and clinicopathology of renal cell carcinoma

Expression of amyloid precursor-like protein 2 (APLP2) in glioblastoma is associated with patient prognosis

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry

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