Loss of HSulf-1: The Missing Link between Autophagy and Lipid Droplets in Ovarian Cancer

Debarshi Roy, Susmita Mondal, Ashwani Khurana, Deok Beom Jung, Robert Hoffmann, Xiaoping He, Eleftheria Kalogera, Thomas Dierks, Edward Hammond, Keith Dredge, Vijayalakshmi Shridhar

Research output: Contribution to journalArticle

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Abstract

Defective autophagy and deranged metabolic pathways are common in cancer; pharmacologic targeting of these two pathways could provide a viable therapeutic option. However, how these pathways are regulated by limited availability of growth factors is still unknown. Our study shows that HSulf-1 (endosulfatase), a known tumor suppressor which attenuates heparin sulfate binding growth factor signaling, also regulates interplay between autophagy and lipogenesis. Silencing of HSulf-1 in OV202 and TOV2223 cells (ovarian cancer cell lines) resulted in increased lipid droplets (LDs), reduced autophagic vacuoles (AVs) and less LC3B puncta. In contrast, HSulf-1 proficient cells exhibit more AVs and reduced LDs. Increased LDs in HSulf-1 depleted cells was associated with increased ERK mediated cPLA2 S505 phosphorylation. Conversely, HSulf-1 expression in SKOV3 cells reduced the number of LDs and increased the number of AVs compared to vector controls. Furthermore, pharmacological (AACOCF3) and ShRNA mediated downregulation of cPLA2 resulted in reduced LDs, and increased autophagy. Finally, in vivo experiment using OV202 Sh1 derived xenograft show that AACOCF3 treatment effectively attenuated tumor growth and LD biogenesis. Collectively, these results show a reciprocal regulation of autophagy and lipid biogenesis by HSulf-1 in ovarian cancer.

Original languageEnglish (US)
Article number41977
JournalScientific Reports
Volume7
DOIs
StatePublished - Feb 7 2017

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Autophagy
Ovarian Neoplasms
Vacuoles
Intercellular Signaling Peptides and Proteins
Neoplasms
Lipogenesis
Metabolic Networks and Pathways
Heterografts
Sulfates
Heparin
Lipid Droplets
Down-Regulation
Cell Count
Phosphorylation
Pharmacology
Lipids
Cell Line
Growth

ASJC Scopus subject areas

  • General

Cite this

Loss of HSulf-1 : The Missing Link between Autophagy and Lipid Droplets in Ovarian Cancer. / Roy, Debarshi; Mondal, Susmita; Khurana, Ashwani; Jung, Deok Beom; Hoffmann, Robert; He, Xiaoping; Kalogera, Eleftheria; Dierks, Thomas; Hammond, Edward; Dredge, Keith; Shridhar, Vijayalakshmi.

In: Scientific Reports, Vol. 7, 41977, 07.02.2017.

Research output: Contribution to journalArticle

Roy, D, Mondal, S, Khurana, A, Jung, DB, Hoffmann, R, He, X, Kalogera, E, Dierks, T, Hammond, E, Dredge, K & Shridhar, V 2017, 'Loss of HSulf-1: The Missing Link between Autophagy and Lipid Droplets in Ovarian Cancer', Scientific Reports, vol. 7, 41977. https://doi.org/10.1038/srep41977
Roy, Debarshi ; Mondal, Susmita ; Khurana, Ashwani ; Jung, Deok Beom ; Hoffmann, Robert ; He, Xiaoping ; Kalogera, Eleftheria ; Dierks, Thomas ; Hammond, Edward ; Dredge, Keith ; Shridhar, Vijayalakshmi. / Loss of HSulf-1 : The Missing Link between Autophagy and Lipid Droplets in Ovarian Cancer. In: Scientific Reports. 2017 ; Vol. 7.
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