The phospholipase DDHD1 as a new target in colorectal cancer therapy

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Experimental and Clinical Cancer Research
Volume37
Issue number1
DOIs
Publication statusPublished - Apr 13 2018

Fingerprint

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

Keywords

  • Citrus-limon nanovesicles
  • Colorectal cancer
  • Phospholipase DDHD1

Cite this

Raimondo, S., Cristaldi, M., Fontana, S., Saieva, L., Monteleone, F., Calabrese, G., ... Alessandro, R. (2018). The phospholipase DDHD1 as a new target in colorectal cancer therapy. Journal of Experimental and Clinical Cancer Research, 37(1), 1-12. https://doi.org/10.1186/s13046-018-0753-z

The phospholipase DDHD1 as a new target in colorectal cancer therapy. / Raimondo, Stefania; Cristaldi, Marta; Fontana, Simona; Saieva, Laura; Monteleone, Francesca; Calabrese, Giovanna; Giavaresi, Gianluca; Parenti, Rosalba; Alessandro, Riccardo.

In: Journal of Experimental and Clinical Cancer Research, Vol. 37, No. 1, 13.04.2018, p. 1-12.

Research output: Contribution to journalArticle

Raimondo, S, Cristaldi, M, Fontana, S, Saieva, L, Monteleone, F, Calabrese, G, Giavaresi, G, Parenti, R & Alessandro, R 2018, 'The phospholipase DDHD1 as a new target in colorectal cancer therapy', Journal of Experimental and Clinical Cancer Research, vol. 37, no. 1, pp. 1-12. https://doi.org/10.1186/s13046-018-0753-z
Raimondo, Stefania ; Cristaldi, Marta ; Fontana, Simona ; Saieva, Laura ; Monteleone, Francesca ; Calabrese, Giovanna ; Giavaresi, Gianluca ; Parenti, Rosalba ; Alessandro, Riccardo. / The phospholipase DDHD1 as a new target in colorectal cancer therapy. In: Journal of Experimental and Clinical Cancer Research. 2018 ; Vol. 37, No. 1. pp. 1-12.
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AU - Calabrese, Giovanna

AU - Giavaresi, Gianluca

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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.

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