ArticleOncogene2021
The newly identified MEK1 tyrosine phosphorylation target MACC1 is druggable by approved MEK1 inhibitors to restrict colorectal cancer metastasis.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- MACC1 Hyperactivates Receptor Tyrosine Kinase Signaling Through Phosphorylation-Dependent Adaptor Activity in Colorectal Cancer Cells.Biomolecules · 2026Article
- The Regulatory Interplay of the Colorectal Cancer Biomarkers MACC1 and IER2 and Its Impact on Metastatic Cancer Survival.Biomolecules · 2026Article
- Gut microbial metabolites in colorectal cancer: dual roles in tumorigenesis, immune crosstalk, and therapeutic innovation.Frontiers in cellular and infection microbiology · 2026Review
- Mitochondria-related genes as prognostic signature of endometrial cancer and the effect of MACC1 on tumor cells.PloS one · 2025Article
- MACC1 revisited - an in-depth review of a master of metastasis.Biomarker research · 2024Review
- Global Proteomics Analysis of Lysophosphatidic Acid Signaling in PC-3 Human Prostate Cancer Cells: Role of CCN1.International journal of molecular sciences · 2024Article
- Review
- MACC1-induced migration in tumors: Current state and perspective.Frontiers in oncology · 2023Review
- Article
- Antiproliferative Effects of Cynara Cardunculus in Colorectal Cancer Cells Are Modulated by the Circadian Clock.International journal of molecular sciences · 2022Article
- MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics.Cancers · 2022Article
- Article
- MACC1 Promotes the Progression and Is a Novel Biomarker for Predicting Immunotherapy Response in Colorectal Cancer.Journal of oncology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer metastasis causes >90% of cancer deaths and remains a major treatment challenge. Here we deciphered the impact of tyrosine phosphorylation of MACC1, a causative driver for cancer metastasis, for cancer cell signaling and novel interventions to restrict cancer metastasis. We identified MACC1 as new MEK1 substrate. MEK1 directly phosphorylates MACC1, leading to accelerated and increased ERK1 activation. Mutating in silico predicted hierarchical MACC1 tyrosine phosphorylation sites abrogates MACC1-induced migration, invasion, and MET expression, a transcriptional MACC1 target. Targeting MEK1 by RNAi or clinically applicable MEK1 inhibitors AZD6244 and GSK1120212 reduces MACC1 tyrosine phosphorylation and restricts MACC1-induced metastasis formation in mice. Although MEK1 levels, contrary to MACC1, are not of prognostic relevance for CRC patients, MEK1 expression was found indispensable for MACC1-induced metastasis. This study identifies MACC1 as new MEK1 substrate for tyrosine phosphorylation decisively impacting cell motility, tumor growth, and metastasis. Thus, MAP kinase signaling is not linear leading to ERK activation, but branches at the level of MEK1. This fundamental finding opens new therapeutic options for targeting the MEK1/MACC1 axis as novel vulnerability in patients at high risk for metastasis. This might be extended from CRC to further solid tumor entities.
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