ArticleJournal of experimental & clinical cancer research : CR2021
Pharmacological targeting PTK6 inhibits the JAK2/STAT3 sustained stemness and reverses chemoresistance of colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Neutralizing dentin sialophosphoprotein facilitates tumor vascular normalization in colorectal cancer by blocking the crosstalk between tumor cells and endothelial cells.Acta pharmaceutica Sinica. B · 2026Article
- [Tumor-secreted dentin sialophosphoprotein induces oxaliplatin resistance in colorectal cancer through an integrin αvβ3-dependent pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Elevated PTK6 expression is associated with tumor immune microenvironment remodeling and predicts poor prognosis in endometrial carcinoma.Frontiers in medicine · 2026Article
- Discovery of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRK/PTK6 inhibitors.European journal of medicinal chemistry · 2025Article
- CANDiT: A machine learning framework for differentiation therapy in colorectal cancer.Cell reports. Medicine · 2025Article
- Decision tree-based machine learning methods for identifying colorectal cancer-associated microRNA signatures and their regulatory networks.Scientific reports · 2025Article
- PTK6 drives HNRNPH1 phase separation to activate autophagy and suppress apoptosis in colorectal cancer.Autophagy · 2025Article
- Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma.Discover oncology · 2025Article
- Inhibition of CCT5-mediated asparagine biosynthesis and anti-PD-L1 produce synergistic antitumor effects in colorectal cancer.Acta pharmaceutica Sinica. B · 2025Article
- Network Pharmacology Study on the Mechanisms ofApplied bionics and biomechanics · 2025Article
- RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.Cell death & disease · 2024Article
- mir-605-3p prevents liver premetastatic niche formation by inhibiting angiogenesis via decreasing exosomal nos3 release in gastric cancer.Cancer cell international · 2024Article
- PTK6: An emerging biomarker for prognosis and immunotherapeutic response in clear cell renal carcinoma (KIRC).Heliyon · 2024Article
- The Role of Autophagy in Human Uveal Melanoma and the Development of Potential Disease Biomarkers and Novel Therapeutic Paradigms.Biomedicines · 2024Review
- Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion.International journal of biological sciences · 2024Article
- In Silico Screening of Multi-Domain Targeted Inhibitors for PTK6: A Strategy Integrating Drug Repurposing and Consensus Docking.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer.Cell death discovery · 2023Article
- Diffusion-enhanced characterization of 3D chromatin structure reveals its linkage to gene regulatory networks and the interactome.Genome research · 2023Article
- Roles of cancer stem cells in gastrointestinal cancers.World journal of stem cells · 2023Review
- Patient-derived xenograft models in cancer therapy: technologies and applications.Signal transduction and targeted therapy · 2023Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChemoresistance is the major cause of chemotherapy failure in patients with colorectal cancer (CRC). Protein tyrosine kinase 6 (PTK6) is aberrantly overexpressed in clinical CRC tissues undergoing chemotherapy. We studied if PTK6 contributed to the chemoresistance of CRC in human and mice.
methodsWe obtained tissue samples from patients with CRC and measured the expression of PTK6 by immunohistochemistry. Gain- and loss-of-function assays were performed to study the biological functions of PTK6. We constructed the FLAG-tagged wild type (WT), kinase-dead, and inhibition-defective recombinant mutants of PTK6 to study the effect phosphorylated activation of PTK6 played on CRC cell stemness and chemoresistance. We used small molecule inhibitor XMU-MP-2 to test the influence of PTK6 on sensitivity of CRC cells to 5-FU/L-OHP in both nude mouse and patient-derived xenograft (PDX) animal models.
resultsPTK6 is overexpressed in CRC tissues and plays a stimulatory role in the proliferation and chemoresistance of CRC cells both in vitro and in vivo. PTK6, especially the phosphorylated PTK6, can promote the stemness of CRC cells through interacting with JAK2 and phosphorylating it to activate the JAK2/STAT3 signaling. Pharmacological inhibition of PTK6 using XMU-MP-2 effectively reduces the stemness property of CRC cells and improves its chemosensitivity to 5-FU/L-OHP in both nude mice subcutaneously implanted tumor model and PDX model constructed with NOD-SCID mice.
conclusionsPTK6 interacts with JAK2 and phosphorylates it to activate JAK2/STAT3 signaling to promote the stemness and chemoresistance of CRC cells. Pharmacological inhibition of PTK6 by small molecule inhibitor dramatically enhances the sensitivity to chemotherapy in nude mice and PDX models.
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