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ESRP1-regulated isoform switching of LRRFIP2 determines metastasis of gastric cancer

Author

Listed:
  • Jihee Lee

    (GILO Institute, GILO Foundation
    CHA University)

  • Kyoungwha Pang

    (GILO Institute, GILO Foundation)

  • Junil Kim

    (Soongsil University)

  • Eunji Hong

    (GILO Institute, GILO Foundation
    Sungkyunkwan University)

  • Jeeyun Lee

    (Samsung Medical Center Sungkyunkwan University School of Medicine)

  • Hee Jin Cho

    (Kyungpook National University
    Samsung Medical Center)

  • Jinah Park

    (GILO Institute, GILO Foundation)

  • Minjung Son

    (GILO Institute, GILO Foundation
    Sungkyunkwan University)

  • Sihyun Park

    (GILO Institute, GILO Foundation)

  • Minjung Lee

    (Medpacto Inc.)

  • Akira Ooshima

    (GILO Institute, GILO Foundation)

  • Kyung-Soon Park

    (CHA University)

  • Han-Kwang Yang

    (Seoul National University Hospital
    Seoul National University)

  • Kyung-Min Yang

    (Medpacto Inc.)

  • Seong-Jin Kim

    (GILO Institute, GILO Foundation
    Medpacto Inc.)

Abstract

Although accumulating evidence indicates that alternative splicing is aberrantly altered in many cancers, the functional mechanism remains to be elucidated. Here, we show that epithelial and mesenchymal isoform switches of leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) regulated by epithelial splicing regulatory protein 1 (ESRP1) correlate with metastatic potential of gastric cancer cells. We found that expression of the splicing variants of LRRFIP2 was closely correlated with that of ESRP1. Surprisingly, ectopic expression of the mesenchymal isoform of LRRFIP2 (variant 3) dramatically increased liver metastasis of gastric cancer cells, whereas deletion of exon 7 of LRRFIP2 by the CRISPR/Cas9 system caused an isoform switch, leading to marked suppression of liver metastasis. Mechanistically, the epithelial LRRFIP2 isoform (variant 2) inhibited the oncogenic function of coactivator-associated arginine methyltransferase 1 (CARM1) through interaction. Taken together, our data reveals a mechanism of LRRFIP2 isoform switches in gastric cancer with important implication for cancer metastasis.

Suggested Citation

  • Jihee Lee & Kyoungwha Pang & Junil Kim & Eunji Hong & Jeeyun Lee & Hee Jin Cho & Jinah Park & Minjung Son & Sihyun Park & Minjung Lee & Akira Ooshima & Kyung-Soon Park & Han-Kwang Yang & Kyung-Min Yan, 2022. "ESRP1-regulated isoform switching of LRRFIP2 determines metastasis of gastric cancer," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33786-9
    DOI: 10.1038/s41467-022-33786-9
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    References listed on IDEAS

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    1. Toshifumi Yae & Kenji Tsuchihashi & Takatsugu Ishimoto & Takeshi Motohara & Momoko Yoshikawa & Go J. Yoshida & Takeyuki Wada & Takashi Masuko & Kaoru Mogushi & Hiroshi Tanaka & Tsuyoshi Osawa & Yasuha, 2012. "Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
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