ArticleThe Journal of biological chemistry2018
The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- The MST4-14-3-3ζ complex promotes pancreatic cancer by activating YAP.Biology direct · 2026Article
- Identification of PKN2 and MOB4 as Coordinators of Collective Cell Migration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of GCKIII kinases STK25 and MST3 mitigates organ lipotoxicity and enhances metabolic resilience under nutritional stress.BMC medicine · 2025Article
- STK26 Promotes the Stabilization of ATF6 to Facilitate the Progression of Colorectal Cancer.International journal of molecular sciences · 2025Article
- The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells.Cell reports · 2025Article
- Decoding gene expression profiles of Hippo signaling pathway components in breast cancer.Molecular biology reports · 2025Article
- STRIPAK, a fundamental signaling hub of eukaryotic development.Microbiology and molecular biology reviews : MMBR · 2024Review
- Pan-cancer analysis of the prognostic and immunological role of hippo-YAP signaling pathway.Discover oncology · 2024Article
- Genetic Ablation of STE20-Type Kinase MST4 Does Not Alleviate Diet-Induced MASLD Susceptibility in Mice.International journal of molecular sciences · 2024Article
- Research on the signaling pathway and the related mechanism of traditional Chinese medicine intervention in chronic gastritis of the "inflammation-cancer transformation".Frontiers in pharmacology · 2024Review
- Review
- Mapping the MOB proteins' proximity network reveals a unique interaction between human MOB3C and the RNase P complex.The Journal of biological chemistry · 2023Article
- Article
- MST4 promotes proliferation, invasion, and metastasis of gastric cancer by enhancing autophagy.Heliyon · 2023Article
- The role of the Hippo pathway in autophagy in the heart.Cardiovascular research · 2023Review
- STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent.Journal of experimental & clinical cancer research : CR · 2023Article
- The profile of expression of the scaffold protein SG2NA(s) differs between cancer types and its interactome in normal vis-a-vis breast tumor tissues suggests its wide roles in regulating multiple cellular pathways.Molecular and cellular biochemistry · 2022Article
- Mob4-dependent STRIPAK involves the chaperonin TRiC to coordinate myofibril and microtubule network growth.PLoS genetics · 2022Article
- Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival.Circulation research · 2022Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian STE20-like protein kinase 1 (MST1)-MOB kinase activator 1 (MOB1) complex has been shown to suppress the oncogenic activity of Yes-associated protein (YAP) in the mammalian Hippo pathway, which is involved in the development of multiple tumors, including pancreatic cancer (PC). However, it remains unclear whether other MST-MOB complexes are also involved in regulating Hippo-YAP signaling and have potential roles in PC. Here, we report that mammalian STE20-like kinase 4 (MST4), a distantly related ortholog of the MST1 kinase, forms a complex with MOB4 in a phosphorylation-dependent manner. We found that the overall structure of the MST4-MOB4 complex resembles that of the MST1-MOB1 complex, even though the two complexes exhibited opposite biological functions in PC. In contrast to the tumor-suppressor effect of the MST1-MOB1 complex, the MST4-MOB4 complex promoted growth and migration of PANC-1 cells. Moreover, expression levels of MST4 and MOB4 were elevated in PC and were positively correlated with each other, whereas MST1 expression was down-regulated. Because of divergent evolution of key interface residues, MST4 and MOB4 could disrupt assembly of the MST1-MOB1 complex through alternative pairing and thereby increased YAP activity. Collectively, these findings identify the MST4-MOB4 complex as a noncanonical regulator of the Hippo-YAP pathway with an oncogenic role in PC. Our findings highlight that although MST-MOB complexes display some structural conservation, they functionally diverged during their evolution.
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