Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53.
Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification.
Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways.
Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316)
Catalytic component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with p53/TP53, SMAD4, STK11IP and WDR6.
Interacts with NR4A1. Interacts with NISCH; this interaction may increase STK11 activity. Interacts with PTEN; leading to PTEN phosphorylation.
Interacts with SIRT1; the interaction deacetylates STK11. Interacts with CDKN1A
Ubiquitously expressed. Strongest expression in testis and fetal liver
An autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer.
A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to STK11IP, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 28
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT05445843 | Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation | Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation. | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT06188208 | Advanced Solid Tumors, Advanced Hematologic Tumors | A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130850 in Participants With Advanced Solid and Hematologic Tumors | PHASE1 | TERMINATED |
| NCT06008093 | Carcinoma, Non-Small-Cell Lung | A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic NSCLC Patients With Non-squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT06712095 | Lynch Syndrome, Li Fraumeni Syndrome, PTEN Hamartoma Syndrome, FAP, MUTYH Biallelic Mutation, STK11 Mutation, CDH1 Gene Mutation, CHEK2 Gene Mutation, BMPR1A Gene Mutation, SMAD4 Gene Mutation | Video Capsule Examination in Patients With Lynch Syndrome | NA | RECRUITING |
| NCT07207395 | Lung Cancer (NSCLC) | A Study of Orally Administered JBI-802 Alone or in Combination With Pembrolizumab for Patients With Non-small Cell Lung Cancer With an STK11 Mutation. | PHASE2 | RECRUITING |
| NCT07017829 | Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8 | GT103 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic STK11 Mutant Non-Small Cell Lung Cancer | PHASE2 | RECRUITING |
| NCT06219174 | Non Small Cell Lung Cancer, Lung Cancer | Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC (DFMO) | PHASE1, PHASE2 | SUSPENDED |
| NCT06124963 | Gastric Type Adenocarcinoma (GAS) With STK11 Mutation | A Study of WX390 Combined With Toripalimab in Patients With Advanced Gastric-type Endocervical Adenocarcinoma With STK11 Mutations | PHASE2 | RECRUITING |
| NCT06494540 | Non-squamous Metastatic Non-Small-Cell Lung Carcinoma | NIS to Examine the Effectiveness of TDC in Patients With Metastatic Non-squamous NSCLC and High-risk Genetic Alterations | N/A | RECRUITING |
| NCT03785249 | Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease | Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1 | PHASE1, PHASE2 | ACTIVE_NOT_RECRUITING |