The Atypical Kinase RIOK1 Promotes Tumor Growth and Invasive Behavior.

EBioMedicine
Florian WeinbergTilman Brummer

Abstract

Despite being overexpressed in different tumor entities, RIO kinases are hardly characterized in mammalian cells. We investigated the role of these atypical kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3, strongly impairs proliferation and invasiveness in conventional and 3D culture systems. Interestingly, these effects were mainly observed in RAS mutant cancer cells. In contrast, growth of RAS wildtype Caco-2 and Bcr-Abl-driven K562 cells is not affected by RIOK1 knockdown, suggesting a specific requirement for RIOK1 in the context of oncogenic RAS signaling. Furthermore, we show that RIOK1 activates NF-κB signaling and promotes cell cycle progression. Using proteomics, we identified the pro-invasive proteins Metadherin and Stathmin1 to be regulated by RIOK1. Additionally, we demonstrate that RIOK1 promotes lung colonization in vivo and that RIOK1 is overexpressed in different subtypes of human lung- and breast cancer. Altogether, our data suggest RIOK1 as a potential therapeutic target, especially in RAS-driven cancers.

Citations

Jul 17, 2018·Nucleic Acids Research·Maria G IacovellaPeter De Wulf
Feb 7, 2019·Proteomics. Clinical Applications·Maria FrantziHarald Mischak
Jul 8, 2020·The Journal of Clinical Investigation·Anqun ChenJohn Cijiang He
Jul 10, 2018·Oncotarget·Alexandra HörmannRalph A Neumüller
May 12, 2018·International Journal of Oncology·Kun LiuMingming Gu
Mar 19, 2020·ACS Medicinal Chemistry Letters·Carrow WellsAlison D Axtman

❮ Previous
Next ❯

Methods Mentioned

BETA
FCS
restriction digest
co-immunoprecipitation
immunoprecipitation
acetylation
Xenografts
xenograft
antibody array
fluorescence imaging
GTPase

Software Mentioned

GraphPad Prism
Fusion
cBioPortal
BIOSS toolbox
ZEISS AxioObserver
STRING
MaxQuant
Photoshop
Perseus

Related Concepts

Related Feeds

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.