Akt-mediated Ephexin1–Ras interaction promotes oncogenic Ras signaling and colorectal and lung cancer cell proliferation

Jeeho Kim, Young Jin Jeon, Sung Chul Lim, Joohyun Ryu, Jung Hee Lee, In Youb Chang, Ho Jin You

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1 Scopus citations

Abstract

Ephexin1 was reported to be highly upregulated by oncogenic Ras, but the functional consequences of this remain poorly understood. Here, we show that Ephexin1 is highly expressed in colorectal cancer (CRC) and lung cancer (LC) patient tissues. Knockdown of Ephexin1 markedly inhibited the cell growth of CRC and LC cells with oncogenic Ras mutations. Ephexin1 contributes to the positive regulation of Ras-mediated downstream target genes and promotes Ras-induced skin tumorigenesis. Mechanically, Akt phosphorylates Ephexin1 at Ser16 and Ser18 (pSer16/18) and pSer16/18 Ephexin1 then interacts with oncogenic K-Ras to promote downstream MAPK signaling, facilitating tumorigenesis. Furthermore, pSer16/18 Ephexin1 is associated with both an increased tumor grade and metastatic cases of CRC and LC, and those that highly express pSer16/18 exhibit poor overall survival rates. These data indicate that Ephexin1 plays a critical role in the Ras-mediated CRC and LC and pSer16/18 Ephexin1 might be an effective therapeutic target for CRC and LC.

Original languageEnglish (US)
Article number1013
JournalCell Death and Disease
Volume12
Issue number11
DOIs
StatePublished - Nov 2021

Bibliographical note

Funding Information:
This work is supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (NRF-2015R1A5A2009070 and NRF-2021R1A2C2005652), and the Ministry of Education (2019R1A6A3A01092483).

Publisher Copyright:
© 2021, The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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