STK11

Overview

STK11 (LKB1) encodes a serine/threonine kinase that acts as a tumor suppressor regulating cell polarity and energy metabolism via the AMPK pathway. Germline STK11 mutations define Peutz-Jeghers syndrome (PJS), which includes elevated gastric cancer risk and must be excluded in familial gastric cancer evaluation.

Alterations observed in the corpus

  • Germline STK11 loss-of-function mutations define Peutz-Jeghers syndrome (PJS), included in the mandatory multigene panel for familial non-hereditary gastric cancer (FNHGC) workup; must be ruled out before FNHGC labeling. PMID:24816255
  • Inactivating mutations in 17% of LUAD (TCGA, n=230); drives mTOR activation via LKB1/AMPK loss; defining co-feature of the PP (proximal-proliferative) transcriptional subtype with KRAS co-mutation. PMID:25079552
  • PI3K/RAS negative regulator with inactivating events in 1–3 of 29 metastatic cSCC samples PMID:25589618
  • Additional cancer-gene lesion identified in KRAS-wildtype pancreatic ductal adenocarcinoma cases (109-case WES cohort). PMID:25855536
  • Low-frequency mutation detected in both PDTC and ATC cohorts in thyroid cancer targeted sequencing PMID:26878173
  • Significantly mutated exclusively in lung ADC vs other TCGA tumor types (q < 0.1); significantly co-occurs with activating KRAS mutations (p = 1.1 × 10⁻⁶) in a 660-ADC exome cohort PMID:27158780.
  • STK11 significantly enriched in the unknown mitogenic driver (UMD) subset of 860 metastatic LUAD patients profiled by MSK-IMPACT (p<0.05); also enriched in heavy-smoker UMD samples; authors nominate STK11 as a candidate targetable mitogenic driver PMID:28336552.
  • Newly nominated CCA driver; mutated in 5%, mostly inactivating (7 nonsense, 9 frameshift mutations) PMID:28667006
  • Used as co-deletion partner with Pten in murine prostate organoid model (Ptenpc-/-;Lkb1pc-/-) for in-vivo NOL10/USF1 knockdown experiments in prostate cancer PMID:28927585
  • Significantly enriched in no-durable-benefit (NDB) vs non-ICI NSCLC (FDR-adjusted P=0.007); consistent with STK11/LKB1-loss-associated low tumor inflammation and reduced response to anti-PD-(L)1 therapy. PMID:29337640
  • One pLoF LP/PV identified: c.179dup p.(Tyr60*) in a boy with congenital Peutz-Jeghers syndrome and T-cell ALL; mother and maternal grandfather also have PJS. Single-cohort OR=199.5 (95% CI 12.5-3195.8, p=0.010) — extreme estimate driven by very low gnomAD baseline (1/74,022 controls) PMID:29489754

Cancer types (linked)

  • STAD – germline STK11 mutations (Peutz-Jeghers syndrome) must be excluded before diagnosing FNHGC; somatic STK11 role in FNHGC tumor biology not separately characterized in this review. PMID:24816255

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity data with specific partner genes reported in the current corpus.

Therapeutic relevance

  • No direct STK11-targeted therapy data reported in the current corpus for gastric cancer.

Open questions

  • Gastric cancer penetrance specifically attributable to STK11/PJS and optimal endoscopic surveillance intervals for STK11 germline carriers remain incompletely characterized.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:25079552

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:25855536

This page was processed by wiki-cli on 2026-05-14. - PMID:26878173

This page was processed by wiki-cli on 2026-05-14. - PMID:27158780

This page was processed by wiki-cli on 2026-05-14. - PMID:28336552

This page was processed by wiki-cli on 2026-05-14. - PMID:28667006

This page was processed by wiki-cli on 2026-05-15. - PMID:28927585

This page was processed by wiki-cli on 2026-05-15. - PMID:29337640

This page was processed by entity-page-writer on 2026-05-15. - PMID:29489754

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