ArticleMolecular cancer2023
The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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11 citing papers in PubMed, 22 citations in OpenAlex.
- Enoxaparin induces apoptosis and autophagy, modulates inflammatory signaling, and reduces oxidative DNA damage in breast and liver cancer cells.Scientific reports · 2026Article
- Exploring platelet-covered and naked circulating tumor cells - a single-cell transcriptomic perspective.Journal of translational medicine · 2026Article
- KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers.Molecular cancer · 2026Review
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Golgi Drivers of Cancer.Sub-cellular biochemistry · 2026Review
- Myc and Skp2 overexpression promotes p27 ubiquitination and degradation in Ewing Sarcoma.PloS one · 2026Article
- A brief history of phosphatidylinositol transfer proteins: from the backwaters of cell biology to prime time in lipid signaling.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- NAP1L1 degradation by FBXW7 reduces the deubiquitination of HDGF-p62 signaling to stimulate autophagy and induce primary cisplatin chemosensitivity in nasopharyngeal carcinoma.Molecular cancer · 2025Article
- Mammalian START-like phosphatidylinositol transfer proteins - Physiological perspectives and roles in cancer biology.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Review
- Multi-omics analyses based on genes associated with oxidative stress and phospholipid metabolism revealed the intrinsic molecular characteristics of pancreatic cancer.Scientific reports · 2023Article
- Correction: The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer.Molecular cancer · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe discovery of functionally relevant KRAS effectors in lung and pancreatic ductal adenocarcinoma (LUAD and PDAC) may yield novel molecular targets or mechanisms amenable to inhibition strategies. Phospholipids availability has been appreciated as a mechanism to modulate KRAS oncogenic potential. Thus, phospholipid transporters may play a functional role in KRAS-driven oncogenesis. Here, we identified and systematically studied the phospholipid transporter PITPNC1 and its controlled network in LUAD and PDAC.
methodsGenetic modulation of KRAS expression as well as pharmacological inhibition of canonical effectors was completed. PITPNC1 genetic depletion was performed in in vitro and in vivo LUAD and PDAC models. PITPNC1-deficient cells were RNA sequenced, and Gene Ontology and enrichment analyses were applied to the output data. Protein-based biochemical and subcellular localization assays were run to investigate PITPNC1-regulated pathways. A drug repurposing approach was used to predict surrogate PITPNC1 inhibitors that were tested in combination with KRASG12C inhibitors in 2D, 3D, and in vivo models.
resultsPITPNC1 was increased in human LUAD and PDAC, and associated with poor patients' survival. PITPNC1 was regulated by KRAS through MEK1/2 and JNK1/2. Functional experiments showed PITPNC1 requirement for cell proliferation, cell cycle progression and tumour growth. Furthermore, PITPNC1 overexpression enhanced lung colonization and liver metastasis. PITPNC1 regulated a transcriptional signature which highly overlapped with that of KRAS, and controlled mTOR localization via enhanced MYC protein stability to prevent autophagy. JAK2 inhibitors were predicted as putative PITPNC1 inhibitors with antiproliferative effect and their combination with KRASG12C inhibitors elicited a substantial anti-tumour effect in LUAD and PDAC.
conclusionsOur data highlight the functional and clinical relevance of PITPNC1 in LUAD and PDAC. Moreover, PITPNC1 constitutes a new mechanism linking KRAS to MYC, and controls a druggable transcriptional network for combinatorial treatments.
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