ArticleNature communications2023
SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- Therapeutic role of caveolin family in stem cell fate and development for management of chronic degenerative diseases: A scientometric study to an in-depth review.Journal of advanced research · 2026Review
- Tumor cell villages define the co-dependency of tumor and microenvironment in liver cancer.Nature communications · 2026Article
- The Implications of Radiotherapy-Induced Cellular Senescence for Cancer Treatment and Tumor Microenvironment Modulation.International journal of biological sciences · 2026Review
- Identification and Validation of Tumorigenesis Related Hub Genes in Hepatocellular Carcinoma via Integrated Bioinformatics Analysis.Iranian journal of biotechnology · 2025Article
- APOA2 mediates immune therapy tolerance in hepatocellular carcinoma by inhibiting the antigen-presenting function of dendritic cells through the PPAR signaling pathway.Translational cancer research · 2025Article
- Unsupervised Clustering Subtype Analysis and Prognostic Risk Model of Cuproptosis-Related Genes for Liver Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Changes in perioperative serum transaminase levels: predicting early recurrence after hepatectomy for hepatocellular carcinoma.Frontiers in oncology · 2025Article
- High SPINK1 Immunostaining in Colorectal Carcinoma is Associated with Poor Outcomes.Sultan Qaboos University medical journal · 2025Article
- Advancing Cancer Biology: Highlights from the 2025 FASEB SRC on Cellular Plasticity in Cancer.Cancer heterogeneity and plasticity · 2025Article
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- SPINK1 facilitates tumor progression via the EGFR/JAK/STAT3 axis in oral squamous cell carcinoma: insights from single-cell RNA sequencing.Frontiers in oncology · 2025Article
- E2F2 Reprograms Macrophage Function By Modulating Material and Energy Metabolism in the Progression of Metabolic Dysfunction-Associated Steatohepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma.Cell reports. Medicine · 2024Article
- The molecular determinants of phenotypic plasticity in homeostasis and neoplasia.Cancer heterogeneity and plasticity · 2024Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Tumor lineage plasticity, considered a hallmark of cancer, denotes the phenomenon in which tumor cells co-opt developmental pathways to attain cellular plasticity, enabling them to evade targeted therapeutic interventions. However, the underlying molecular events remain largely elusive. Our recent study identified CD133/Prom1 in hepatocellular carcinoma (HCC) tumors to mark proliferative tumor-propagating cells with cancer stem cell-like properties, that follow a dedifferentiation trajectory towards a more embryonic state. Here we show SPINK1 to strongly associate with CD133 + HCC, and tumor dedifferentiation. Enhanced transcriptional activity of SPINK1 is mediated by promoter binding of ELF3, which like CD133, is found to increase following 5-FU and cisplatin treatment; while targeted depletion of CD133 will reduce both ELF3 and SPINK1. Functionally, SPINK1 overexpression promotes tumor initiation, self-renewal, and chemoresistance by driving a deregulated EGFR-ERK-CDK4/6-E2F2 signaling axis to induce dedifferentiation of HCC cells into their ancestral lineages. Depleting SPINK1 function by neutralizing antibody treatment or in vivo lentivirus-mediated Spink1 knockdown dampens HCC cancer growth and their ability to resist chemotherapy. Targeting oncofetal SPINK1 may represent a promising therapeutic option for HCC treatment.
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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.