4.0 Article

Pirin delocalization in melanoma progression identified by high content immuno-detection based approaches

Journal

BMC CELL BIOLOGY
Volume 11, Issue -, Pages -

Publisher

BIOMED CENTRAL LTD
DOI: 10.1186/1471-2121-11-5

Keywords

-

Categories

Funding

  1. Associazione Italiana per la Ricerca sul Cancro (AIRC)
  2. Fondazione CARIPLO

Ask authors/readers for more resources

Background: Pirin (PIR) is a highly conserved nuclear protein originally isolated as an interactor of NFI/CTF1 transcription/replication factor. It is a member of the functionally diverse cupin superfamily and its activity has been linked to different biological and molecular processes, such as regulation of transcription, apoptosis, stress response and enzymatic processes. Although its precise role in these functions has not yet been defined, PIR expression is known to be deregulated in several human malignancies. Results: We performed immunohistochemical analysis of PIR expression in primary samples from normal human tissues and tumors and identified a dislocation of PIR to the cytoplasm in a subset of melanomas, and a positive correlation between cytoplasmic PIR levels and melanoma progression. PIR localization was subsequently analyzed in vitro in melanoma cell lines through a high content immunofluorescence based approach (ImmunoCell-Array). Conclusions: The high consistency between in vivo and in vitro results obtained by immunohistochemistry and ImmunoCell-Array provides a validation of the potential of ImmunoCell-Array technology for the rapid screening of putative biological markers, and suggests that cytoplasmic localization of PIR may represent a characteristic of melanoma progression.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.0
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemical Research Methods

Modeling cell proliferation in human acute myeloid leukemia xenografts

Marco S. Nobile, Thalia Vlachou, Simone Spolaor, Daniela Bossi, Paolo Cazzaniga, Luisa Lanfrancone, Giancarlo Mauri, Pier Giuseppe Pelicci, Daniela Besozzr

BIOINFORMATICS (2019)

Article Oncology

Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis

Mohamed Elgendy, Marco Ciro, Amir Hosseini, Jakob Weiszmann, Luca Mazzarella, Elisa Ferrari, Riccardo Cazzoli, Giuseppe Curigliano, Andrea DeCensi, Bernardo Bonanni, Alfredo Budillon, Pier Giuseppe Pelicci, Veerle Janssens, Manfred Ogris, Manuela Baccarini, Luisa Lanfrancone, Wolfram Weckwerth, Marco Foiani, Saverio Minucci

CANCER CELL (2019)

Meeting Abstract Oncology

The ACC melanoma pilot project: Real-world evaluation of an NGS platform for molecular characterization of melanoma in Italy.

Ivan Molineris, Lauretta Levati, Enrico Berrino, Stefania D'Atri, Chiara Menin, Gabriele Madonna, Jenny Bulgarelli, Paola Ghiorzo, Virginia Ferraresi, Tiziana Venesio, Licia Rivoltini, Monica Rodolfo, Luisa Lanfrancone, Luca Mazzarella, Alessandro Guida, Pier Giuseppe Pelicci, Ruggero De Maria, Paolo Antonio Ascierto, Enzo Medico, Giandomenico Russo

JOURNAL OF CLINICAL ONCOLOGY (2019)

Article Biology

The chromodomain helicase CHD4 regulates ERBB2 signaling pathway and autophagy in ERBB2+ breast cancer cells

Carolina D'Alesio, Grazia Bellese, Maria Cristina Gagliani, Anastasia Lechiara, Martina Dameri, Elena Grasselli, Luisa Lanfrancone, Katia Cortese, Patrizio Castagnola

BIOLOGY OPEN (2019)

Article Genetics & Heredity

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Xing Yi Woo, Jessica Giordano, Anuj Srivastava, Zi-Ming Zhao, Michael W. Lloyd, Roebi de Bruijn, Yun-Suhk Suh, Rajesh Patidar, Li Chen, Sandra Scherer, Matthew H. Bailey, Chieh-Hsiang Yang, Emilio Cortes-Sanchez, Yuanxin Xi, Jing Wang, Jayamanna Wickramasinghe, Andrew V. Kossenkov, Vito W. Rebecca, Hua Sun, R. Jay Mashl, Sherri R. Davies, Ryan Jeon, Christian Frech, Jelena Randjelovic, Jacqueline Rosains, Francesco Galimi, Andrea Bertotti, Adam Lafferty, Alice C. O'Farrell, Elodie Modave, Diether Lambrechts, Petra ter Brugge, Violeta Serra, Elisabetta Marangoni, Rania El Botty, Hyunsoo Kim, Jong-Il Kim, Han-Kwang Yang, Charles Lee, Dennis A. Dean, Brandi Davis-Dusenbery, Yvonne A. Evrard, James H. Doroshow, Alana L. Welm, Bryan E. Welm, Michael T. Lewis, Bingliang Fang, Jack A. Roth, Funda Meric-Bernstam, Meenhard Herlyn, Michael A. Davies, Li Ding, Shunqiang Li, Ramaswamy Govindan, Claudio Isella, Jeffrey A. Moscow, Livio Trusolino, Annette T. Byrne, Jos Jonkers, Carol J. Bult, Enzo Medico, Jeffrey H. Chuang

Summary: The analysis of copy number alterations in patient-derived xenografts (PDXs) and matched patient tumor samples reveals strong conservation of copy number alterations from patient tumors through late-passage PDXs, without systematic evolution driven by the mouse host. This suggests that PDX models are accurate in representing human cancer and that the mouse host does not significantly impact the copy number alterations during tumor evolution within the PDX model.

NATURE GENETICS (2021)

Article Biochemistry & Molecular Biology

Long non-coding RNA TINCR suppresses metastatic melanoma dissemination by preventing ATF4 translation

Marine Melixetian, Daniela Bossi, Marija Mihailovich, Simona Punzi, Iros Barozzi, Federica Marocchi, Alessandro Cuomo, Tiziana Bonaldi, Giuseppe Testa, Jean-Christophe Marine, Eleonora Leucci, Saverio Minucci, Pier Giuseppe Pelicci, Luisa Lanfrancone

Summary: The study found that the lncRNA TINCR is down-regulated in metastatic melanoma and its silencing increases invasive markers expression, migration, tumor growth, and resistance to inhibitors. ATF4 plays a key role in this process by regulating translational reprogramming. Re-expression of TINCR suppresses the invasive phenotype, reduces tumor-initiating cells and metastasis, and increases drug sensitivity in metastatic melanoma.

EMBO REPORTS (2021)

Review Cell Biology

Regulation of LncRNAs in Melanoma and Their Functional Roles in the Metastatic Process

Marine Melixetian, Pier Giuseppe Pelicci, Luisa Lanfrancone

Summary: Long non-coding RNAs play crucial roles in melanoma growth and spreading, and can be used as biomarkers for disease diagnosis and patient prognosis.

CELLS (2022)

Article Cell Biology

Targeting the USP7/RRM2 axis drives senescence and sensitizes melanoma cells to HDAC/LSD1 inhibitors

Letizia Granieri, Federica Marocchi, Marine Melixetian, Neda Mohammadi, Paola Nicoli, Alessandro Cuomo, Tiziana Bonaldi, Stefano Confalonieri, Federica Pisati, Giuseppina Giardina, Giovanni Bertalot, Daniela Bossi, Luisa Lanfrancone

Summary: This study identifies USP7 as a regulator of melanoma and shows that its downregulation induces cellular senescence, inhibiting tumor growth and proliferation. Transcriptomic and proteomic analysis reveals the targets and networks affected by USP7 depletion. RRM2 is identified as a target of USP7 and is regulated by USP7 during the S phase of the cell cycle. Combination therapy using a USP7 inhibitor and a histone deacetylase (HDAC)/LSD1 inhibitor eliminates senescent cells.

CELL REPORTS (2022)

Article Biology

DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness

Arnaud Carrier, Cecile Desjobert, Loic Ponger, Laurence Lamant, Matias Bustos, Jorge Torres-Ferreira, Rui Henrique, Carmen Jeronimo, Luisa Lanfrancone, Audrey Delmas, Gilles Favre, Antoine Daunay, Florence Busato, Dave S. B. Hoon, Jorg Tost, Chantal Etievant, Joelle Riond, Paola B. Arimondo

Summary: This study identified 229 differentially hypermethylated genes in aggressive melanoma cell lines, and eight hypermethylated gene promoters were validated in tissues from melanoma patients. Additionally, five identified CpGs from primary melanoma tissues were transformed into a DNA methylation score that can predict patient survival. This strategy has the potential to be applied to other diseases with DNA methylation alterations.

ELIFE (2022)

Article Cell Biology

Targeting the MITF/APAF-1 axis as salvage therapy for MAPK inhibitors in resistant melanoma

Pietro Carotenuto, Alessia Romano, Anna Barbato, Paola Quadrano, Simona Brillante, Mariagrazia Volpe, Luigi Ferrante, Roberta Tammaro, Manuela Morleo, Rossella De Cegli, Antonella Iuliano, Marialuisa Testa, Fabrizio Andreone, Gennaro Ciliberto, Eduardo Clery, Giancarlo Troncone, Giuseppe Palma, Claudio Arra, Antonio Barbieri, Mariaelena Capone, Gabriele Madonna, Paolo A. Ascierto, Luisa Lanfrancone, Alessia Indrieri, Brunella Franco

Summary: This study identifies the MITF/APAF-1 axis as a molecular driver of MAPK inhibitor resistance in melanoma, and quinacrine and methylbenzethonium as potent activators of apoptosis and suppressors of MITF function, demonstrating their potential as therapeutic approaches for resistant melanoma.

CELL REPORTS (2022)

Article Oncology

Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells

Arnaud Carrier, Cecile Desjobert, Valerie Lobjois, Lise Rigal, Florence Busato, Jorg Tost, Miquel Ensenyat-Mendez, Diego M. Marzese, Anne Pradines, Gilles Favre, Laurence Lamant, Luisa Lanfrancone, Chantal Etievant, Paola B. Arimondo, Joelle Riond

Summary: Protocadherin proteins play an important role in cell adhesion and signaling pathways. The study found that the PCDHB15 gene's specific exon is hypermethylated in melanoma, leading to its silencing. This silencing contributes to the aggressiveness of melanoma.

CLINICAL EPIGENETICS (2022)

Article Biochemistry & Molecular Biology

BS148 Reduces the Aggressiveness of Metastatic Melanoma via Sigma-2 Receptor Targeting

Claudia Sorbi, Silvia Belluti, Claudio Giacinto Atene, Federica Marocchi, Pasquale Linciano, Neena Roy, Elia Paradiso, Livio Casarini, Simone Ronsisvalle, Tommaso Zanocco-Marani, Livio Brasili, Luisa Lanfrancone, Carol Imbriano, Giulia Di Rocco, Silvia Franchini

Summary: The management of advanced-stage melanoma is challenging due to resistance to current therapies. Therefore, developing alternative strategies is important. Recent research has identified a potent S2R modulator (BS148) that effectively targets melanoma. Mechanistic studies revealed that BS148 activates the endoplasmic reticulum stress response and downregulates genes related to the cholesterol pathway and activates the MAPK signaling pathway. Furthermore, BS148 treatment reduces melanoma cell viability and migration in patient-derived xenograft (PDX) cells, demonstrating its potential as a promising therapeutic target for cancer treatment.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Dermatology

Actionable Genetic Screens Unveil Targeting of AURKA, MEK, and Fatty Acid Metabolism as an Alternative Therapeutic Approach for Advanced Melanoma

Federica Marocchi, Fernando Palluzzi, Paola Nicoli, Marine Melixetian, Giulia Lovati, Giovanni Bertalot, Salvatore Pece, Pier Francesco Ferrucci, Daniela Bossi, Luisa Lanfrancone

Summary: Despite improvements in the management of metastatic melanoma, there are still patients who do not respond to current therapies. Through a preclinical assay, researchers identified a combination therapy targeting AURKA and MAPK/extracellular signal-regulated kinase kinase that was highly effective in metastatic melanoma. Addition of a fatty acid oxidation inhibitor further improved treatment outcomes.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2023)

Article Oncology

ShcD Binds DOCK4, Promotes Ameboid Motility and Metastasis Dissemination, Predicting Poor Prognosis in Melanoma

Ewa Aladowicz, Letizia Granieri, Federica Marocchi, Simona Punzi, Giuseppina Giardina, Pier Francesco Ferrucci, Giovanni Mazzarol, Maria Capra, Giuseppe Viale, Stefano Confalonieri, Sara Gandini, Fiorenza Lotti, Luisa Lanfrancone

CANCERS (2020)

Article Oncology

WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells

Simona Punzi, Chiara Balestrieri, Carolina D'Alesio, Daniela Bossi, Gaetano Ivan Dellino, Elena Gatti, Giancarlo Pruneri, Carmen Criscitiello, Giulia Lovati, Marine Meliksetyan, Alessandro Carugo, Giuseppe Curigliano, Gioacchino Natoli, Pier Giuseppe Pelicci, Luisa Lanfrancone

BREAST CANCER RESEARCH (2019)

No Data Available