ArticleOncogene2018
SOX9 activity is induced by oncogenic Kras to affect MDC1 and MCMs expression in pancreatic cancer.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- The Clinicopathological and Prognostic Significance of SOX9 Expression in Gastric Cancer: Meta-Analysis and TCGA Analysis.Frontiers in oncology · 2021Pooled it
- Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review).Oncology reports · 2026Review
- The complex interplay between diabetes mellitus and pancreatic carcinogenesis: deciphering multifactorial mechanisms and identifying emerging therapeutic vulnerabilities.Cell & bioscience · 2025Review
- RACK1 attenuates pancreatic tumorigenesis by suppressing acinar-to-ductal metaplasia through inflammatory signaling modulation.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Targeting MCM10 disrupts cancer stemness and counteracts sorafenib resistance in hepatocellular carcinoma.Cancer gene therapy · 2025Article
- Deep Reinforcement Learning for CT-Based Non-Invasive Prediction of SOX9 Expression in Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2025Article
- Deciphering of SOX9 Functions in Pancreatic Cancer Cells.International journal of molecular sciences · 2025Article
- Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9.Biology direct · 2025Article
- Retinoic acid receptor-β deletion in a model of early pancreatic ductal adenocarcinoma (PDAC) tumorigenesis.American journal of cancer research · 2025Article
- SOX9 drives KRAS-induced lung adenocarcinoma progression and suppresses anti-tumor immunity.Oncogene · 2023Article
- GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process.International journal of molecular sciences · 2023Article
- SOX9 Protein in Pancreatic Cancer Regulates Multiple Cellular Networks in a Cell-Specific Manner.Biomedicines · 2022Article
- Molecular signaling in pancreatic ductal metaplasia: emerging biomarkers for detection and intervention of early pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells.Molecules (Basel, Switzerland) · 2022Article
- KRAS mutation-independent downregulation of MAPK/PI3K signaling in colorectal cancer.Molecular oncology · 2022Article
- Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas.Blood · 2022Article
- Article
- SOX9 modulates cancer biomarker and cilia genes in pancreatic cancer.Human molecular genetics · 2021Article
- Review
- The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
SRY (sex determining region Y)-box 9 (SOX9) is required for oncogenic Kras-mediated acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasias (PanINs) and ultimately pancreatic ductal adenocarcinoma (PDAC). However, how oncogenic Kras affects SOX9 activity is not yet understood, and SOX9-associated genes in PDAC are also unknown at all. Here, we investigated the mechanistic link between SOX9 and oncogenic Kras, studied biological function of SOX9, and identified SOX9-related genes and their clinical significance in patients with PDAC. Our studies reveal that oncogenic Kras induces SOX9 mRNA and protein expression as well as phosphorylated SOX9 expression in human pancreatic ductal progenitor cells (HPNE) and pancreatic ductal cells (HPDE). Moreover, oncogenic Kras promoted nuclear translocation and transcriptional activity of SOX9 in these cells. TAK1/IκBα/NF-κB pathway contributed to induction of SOX9 by oncogenic Kras, and SOX9 in turn enhanced NF-κB activation. SOX9 promoted the proliferation of HPNE and PDAC cells, and correlated with minichromosome maintenance complex components (MCMs) and mediator of DNA damage checkpoint 1 (MDC1) expression. The overexpressive MDC1 was associated with less perineural and lymph node invasion of tumors and early TNM-stage of patients. Our results indicate that oncogenic Kras induces constitutive activation of SOX9 in HPNE and HPDE cells, and Kras/TAK1/IκBα/NF-κB pathway and a positive feedback between SOX9 and NF-κB are involved in this inducing process. SOX9 accelerates proliferation of cells and affects MCMs and MDC1 expression. MDC1 is associated negatively with invasion and metastasis of PDAC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.