The phospholipase DDHD1 as a new target in colorectal cancer therapy

Marta Cristaldi, Riccardo Alessandro, Simona Fontana, Laura Saieva, Stefania Raimondo, Francesca Monteleone, Rosalba Parenti, Giovanna Calabrese, Riccardo Alessandro, Gianluca Giavaresi

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1 Citazione (Scopus)

Abstract

Background: Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer. Methods: DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional role of DDHD1 in colorectal cancer cell growth. Quantitative proteomics using SWATH-MS was performed to determinate the molecular effects induced by DDHD1 silencing in colorectal cancer cells. Results: The results indicate that DDHD1 supports colon cancer cell proliferation and survival, since its downregulation reduces in vitro colon cancer cell viability and increases apoptosis rate, without affecting normal cells. On the contrary, in vivo studies demonstrate that the xenograft tumors, derived from DDHD1-overexpressing cells, have a higher proliferation rate compared to control animals. Additionally, we found that functional categories, significantly affected by DDHD1 silencing, were specifically related to cancer phenotype and for the first time associated to DDHD1 activity. Conclusions: In conclusion, this study provides the first evidence confirming the role of DDHD1 in cancer, providing a possibility to define a new target to design more effective therapies for colon cancer patients.
Lingua originaleEnglish
pagine (da-a)82-
Numero di pagine12
RivistaJOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume37
Stato di pubblicazionePublished - 2018

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Phospholipases
Colorectal Neoplasms
Colonic Neoplasms
Therapeutics
Cell Survival
Down-Regulation
Protein Domains
Neoplasms
Citrus
Nervous System Diseases
Heterografts
Proteomics
Up-Regulation
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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title = "The phospholipase DDHD1 as a new target in colorectal cancer therapy",
abstract = "Background: Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer. Methods: DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional role of DDHD1 in colorectal cancer cell growth. Quantitative proteomics using SWATH-MS was performed to determinate the molecular effects induced by DDHD1 silencing in colorectal cancer cells. Results: The results indicate that DDHD1 supports colon cancer cell proliferation and survival, since its downregulation reduces in vitro colon cancer cell viability and increases apoptosis rate, without affecting normal cells. On the contrary, in vivo studies demonstrate that the xenograft tumors, derived from DDHD1-overexpressing cells, have a higher proliferation rate compared to control animals. Additionally, we found that functional categories, significantly affected by DDHD1 silencing, were specifically related to cancer phenotype and for the first time associated to DDHD1 activity. Conclusions: In conclusion, this study provides the first evidence confirming the role of DDHD1 in cancer, providing a possibility to define a new target to design more effective therapies for colon cancer patients.",
author = "Marta Cristaldi and Riccardo Alessandro and Simona Fontana and Laura Saieva and Stefania Raimondo and Francesca Monteleone and Rosalba Parenti and Giovanna Calabrese and Riccardo Alessandro and Gianluca Giavaresi",
year = "2018",
language = "English",
volume = "37",
pages = "82--",
journal = "JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH",
issn = "1756-9966",

}

TY - JOUR

T1 - The phospholipase DDHD1 as a new target in colorectal cancer therapy

AU - Cristaldi, Marta

AU - Alessandro, Riccardo

AU - Fontana, Simona

AU - Saieva, Laura

AU - Raimondo, Stefania

AU - Monteleone, Francesca

AU - Parenti, Rosalba

AU - Calabrese, Giovanna

AU - Alessandro, Riccardo

AU - Giavaresi, Gianluca

PY - 2018

Y1 - 2018

N2 - Background: Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer. Methods: DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional role of DDHD1 in colorectal cancer cell growth. Quantitative proteomics using SWATH-MS was performed to determinate the molecular effects induced by DDHD1 silencing in colorectal cancer cells. Results: The results indicate that DDHD1 supports colon cancer cell proliferation and survival, since its downregulation reduces in vitro colon cancer cell viability and increases apoptosis rate, without affecting normal cells. On the contrary, in vivo studies demonstrate that the xenograft tumors, derived from DDHD1-overexpressing cells, have a higher proliferation rate compared to control animals. Additionally, we found that functional categories, significantly affected by DDHD1 silencing, were specifically related to cancer phenotype and for the first time associated to DDHD1 activity. Conclusions: In conclusion, this study provides the first evidence confirming the role of DDHD1 in cancer, providing a possibility to define a new target to design more effective therapies for colon cancer patients.

AB - Background: Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer. Methods: DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional role of DDHD1 in colorectal cancer cell growth. Quantitative proteomics using SWATH-MS was performed to determinate the molecular effects induced by DDHD1 silencing in colorectal cancer cells. Results: The results indicate that DDHD1 supports colon cancer cell proliferation and survival, since its downregulation reduces in vitro colon cancer cell viability and increases apoptosis rate, without affecting normal cells. On the contrary, in vivo studies demonstrate that the xenograft tumors, derived from DDHD1-overexpressing cells, have a higher proliferation rate compared to control animals. Additionally, we found that functional categories, significantly affected by DDHD1 silencing, were specifically related to cancer phenotype and for the first time associated to DDHD1 activity. Conclusions: In conclusion, this study provides the first evidence confirming the role of DDHD1 in cancer, providing a possibility to define a new target to design more effective therapies for colon cancer patients.

UR - http://hdl.handle.net/10447/288234

UR - http://www.jeccr.com/

M3 - Article

VL - 37

SP - 82-

JO - JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

JF - JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

SN - 1756-9966

ER -