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

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 Yang, Seong Jin Kim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number6274
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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