Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells

Victoria O. Shender (), Ksenia S. Anufrieva, Polina V. Shnaider, Georgij P. Arapidi, Marat S. Pavlyukov, Olga M. Ivanova, Irina K. Malyants, Grigory A. Stepanov, Evgenii Zhuravlev, Rustam H. Ziganshin, Ivan O. Butenko, Olga N. Bukato, Ksenia M. Klimina, Vladimir A. Veselovsky, Tatiana V. Grigorieva, Sergey Y. Malanin, Olga I. Aleshikova, Andrey V. Slonov, Nataliya A. Babaeva, Lev A. Ashrafyan, Elena Khomyakova, Evgeniy G. Evtushenko, Maria M. Lukina, Zixiang Wang, Artemiy S. Silantiev, Anna A. Nushtaeva, Daria D. Kharlampieva, Vassili N. Lazarev, Arseniy I. Lashkin, Lorine K. Arzumanyan, Irina Yu. Petrushanko, Alexander A. Makarov, Olga S. Lebedeva, Alexandra N. Bogomazova, Maria A. Lagarkova and Vadim M. Govorun
Additional contact information
Victoria O. Shender: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Ksenia S. Anufrieva: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Polina V. Shnaider: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Georgij P. Arapidi: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Marat S. Pavlyukov: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Olga M. Ivanova: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Irina K. Malyants: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Grigory A. Stepanov: Siberian Branch, Russian Academy of Sciences
Evgenii Zhuravlev: Siberian Branch, Russian Academy of Sciences
Rustam H. Ziganshin: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Ivan O. Butenko: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Olga N. Bukato: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Ksenia M. Klimina: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Vladimir A. Veselovsky: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Tatiana V. Grigorieva: Kazan Federal University
Sergey Y. Malanin: Kazan Federal University
Olga I. Aleshikova: Gynaecology and Perinatal Medicine named after V.I. Kulakov
Andrey V. Slonov: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Nataliya A. Babaeva: Gynaecology and Perinatal Medicine named after V.I. Kulakov
Lev A. Ashrafyan: Gynaecology and Perinatal Medicine named after V.I. Kulakov
Elena Khomyakova: Exosome Analytics
Evgeniy G. Evtushenko: Faculty of Chemistry; Lomonosov Moscow State University
Maria M. Lukina: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Zixiang Wang: Shandong University; Jinan
Artemiy S. Silantiev: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Anna A. Nushtaeva: Siberian Branch, Russian Academy of Sciences
Daria D. Kharlampieva: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Vassili N. Lazarev: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Arseniy I. Lashkin: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Lorine K. Arzumanyan: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Irina Yu. Petrushanko: Russian Academy of Sciences
Alexander A. Makarov: Russian Academy of Sciences
Olga S. Lebedeva: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Alexandra N. Bogomazova: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Maria A. Lagarkova: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical and Biological Agency
Vadim M. Govorun: Research Institute for Systems Biology and Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-26

Abstract: Abstract Ovarian cancer often develops resistance to conventional therapies, hampering their effectiveness. Here, using ex vivo paired ovarian cancer ascites obtained before and after chemotherapy and in vitro therapy-induced secretomes, we show that molecules secreted by ovarian cancer cells upon therapy promote cisplatin resistance and enhance DNA damage repair in recipient cancer cells. Even a short-term incubation of chemonaive ovarian cancer cells with therapy-induced secretomes induces changes resembling those that are observed in chemoresistant patient-derived tumor cells after long-term therapy. Using integrative omics techniques, we find that both ex vivo and in vitro therapy-induced secretomes are enriched with spliceosomal components, which relocalize from the nucleus to the cytoplasm and subsequently into the extracellular vesicles upon treatment. We demonstrate that these molecules substantially contribute to the phenotypic effects of therapy-induced secretomes. Thus, SNU13 and SYNCRIP spliceosomal proteins promote therapy resistance, while the exogenous U12 and U6atac snRNAs stimulate tumor growth. These findings demonstrate the significance of spliceosomal network perturbation during therapy and further highlight that extracellular signaling might be a key factor contributing to the emergence of ovarian cancer therapy resistance.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49512-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49512-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49512-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().