MAP2K4

Overview

MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) is a dual-specificity kinase in the JNK/SAPK stress-response pathway. Recurrent deletions, including homozygous deletions, in breast cancer — particularly ER-positive cases — support a tumor suppressor role. MAP2K4 loss may contribute to unchecked proliferation and resistance to apoptotic stimuli.

Alterations observed in the corpus

  • MAP2K4 (17p11) harbors recurrent deletions with outlying expression in predominantly ER-positive breast cancer cases in the METABRIC cohort (~2,000 tumors); confirmed homozygous deletions were identified, supporting tumor suppressor classification PMID:22522925
  • Identified as a recessive cancer gene with inactivating mutations in breast cancer WES (100 tumors, Sanger cohort); functions as a downstream target of MAP3K1 in the JUN kinase signalling pathway PMID:22722201
  • Inactivating mutations in Luminal A breast cancer (12% of Luminal A tumors combined with MAP3K1); acts in the p38/JNK1 pathway; mutually exclusive with MAP3K1 mutations PMID:23000897
  • Significantly mutated gene in pancreatic ductal adenocarcinoma (ICGC, 142 tumors); novel finding involving Toll-like receptor/MAPK signaling PMID:23103869
  • MAP2K4 identified as a mutation-driver in breast cancer in a 2,433-tumor whole-genome/exome sequencing study (METABRIC/ICGC cohort) PMID:27161491
  • Identified as a significantly mutated driver in metastatic breast cancer (mBC), also recurrent in early-stage breast cancer; enriched among HR+/HER2− mBC drivers PMID:28027327
  • Newly nominated cholangiocarcinoma (CCA) tumor suppressor; homozygous deletions in 2 fluke-positive cases plus 2.2% mutation rate (half inactivating), consistent with tumor-suppressor role PMID:28667006
  • Identified as a novel recurrently mutated gene in metastatic colorectal cancer (mCRC) via MSK-IMPACT targeted sequencing of 1,152 patients PMID:29316426

Cancer types (linked)

  • BRCA (Breast cancer): Recurrent deletions (including homozygous) enriched in ER-positive cases; expression outlier analysis confirmed cis-acting loss of expression PMID:22522925

Co-occurrence and mutual exclusivity

  • Genomic losses occur in ER-positive (luminal) breast cancer subtypes within the METABRIC IntClust framework PMID:22522925

Therapeutic relevance

  • No direct therapeutic agents targeting MAP2K4 are described in the corpus. Loss of MAP2K4 may alter downstream JNK signaling, which is under investigation as a context-dependent therapeutic target.

Open questions

  • The precise mechanisms by which MAP2K4 deletion promotes tumor progression in ER-positive breast cancer and the potential for synthetic lethality with MAP2K4 loss remain to be determined.

Sources

This page was processed by entity-page-writer on 2026-05-06. - PMID:22722201

This page was processed by wiki-cli on 2026-05-06. - PMID:23000897

This page was processed by wiki-cli on 2026-05-06. - PMID:23103869

This page was processed by wiki-cli on 2026-05-06. - PMID:27161491

This page was processed by entity-page-writer on 2026-05-15. - PMID:28667006

This page was processed by wiki-cli on 2026-05-15. - PMID:29316426

This page was processed by wiki-cli on 2026-05-15.