MAP3K13

Overview

MAP3K13 (also known as LZK) is a serine/threonine kinase that functions in the JUN kinase signalling cascade. It phosphorylates and activates MAP2K7, transmitting upstream signals to JNK. In breast cancer, MAP3K13 harbours truncating and non-synonymous mutations, implicating it as a tumour suppressor whose inactivation contributes to abrogation of JUN kinase signalling alongside MAP3K1 and MAP2K4.

Alterations observed in the corpus

• Truncating and non-synonymous mutations identified in breast cancer WES (100 tumors, Sanger cohort); activates MAP2K7 in the JUN kinase pathway PMID:22722201
• MAP3K13 harbors inactivating mutations in ESCC, contributing to MAPK pathway dysregulation PMID:24686850

Cancer types (linked)

• BRCA: Truncating and non-synonymous mutations observed; contributes to JUN kinase pathway inactivation in a subset of breast cancers alongside MAP3K1 and MAP2K4 mutations PMID:22722201

Co-occurrence and mutual exclusivity

• Co-occurs with MAP3K1 and MAP2K4 mutations in a subset of breast cancers; together these genes contribute to JUN kinase pathway inactivation in approximately half of breast cancers PMID:22722201

Therapeutic relevance

• JUN kinase pathway inactivation via MAP3K13 (and MAP3K1/MAP2K4) mutations may represent a therapeutic vulnerability in breast cancer, though specific targeted agents have not yet been clinically validated PMID:22722201

Open questions

• Functional consequences of specific MAP3K13 mutations in breast cancer remain incompletely characterized.
• The biological downstream effects of JUN kinase pathway inactivation in breast cancer are not yet fully understood PMID:22722201

Sources

• PMID:22722201 — Breast cancer WES, 100 tumors, Sanger cohort; driver landscape study.

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