Keywords：Tumor microenvironment, cancer-associated fibroblasts, extracellular matrices, cellular stresses, therapy resistance, tumor initiation and metastasis

1. Targeting pancreatic cancer cell stemness by blocking fibronectin-binding integrins on cancer-associated 

fibroblasts. Cancer Research Communications. 2025

2. Tumor-initiating cells establish a niche to overcome isolation stress.  Trends in Cell Biology. 2024   

3. Integrin αvβ3 Upregulation in Response to Nutrient Stress Promotes Lung Cancer Cell Metabolic Plasticity. 

Cancer Research. 2024  

4. Upregulation of fibronectin and its integrin receptors - an adaptation to isolation stress that facilitates tumor 

initiation. Journal of Cell Science. 2023  

5. Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche

 and support tumour initiation.  Nature Cell Biology.  2023  

6. Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence

 and Enhances Anti-tumor Activity. Cell Stem Cell.  2020  

7. Oxidative stress enhances tumorigenicity and stem-like features via the activation of the Wnt/β-catenin/MYC/Sox2 

axis in ALK-positive anaplastic large-cell lymphoma. BMC Cancer. 2018 

8. A positive feedback loop involving the Wnt/β-catenin/MYC/Sox2 axis defines a highly tumorigenic cell 

subpopulation in ALK-positive anaplastic large cell lymphoma. Journal of Hematology and Oncology. 2016 

9. The PI3K/AKT/c-MYC axis promotes the acquisition of cancer stem-like features in esophageal squamous

 cell carcinoma. Stem Cells. 2016 

10. STAT1 is phosphorylated and downregulated by the oncogenic tyrosine kinase NPM-ALK in ALK-positive 

anaplastic large-cell lymphoma. Blood. 2015 

We are particularly interested in understanding the roles of the tumor microenvironment, encompassing cancer-associated fibroblasts, immune cells, extracellular matrices, and various cellular stresses, in the initiation, progression, and metastasis of pancreatic tumors. In our lab, we employ diverse models, including patient-derived cell lines, organoids, transgenic mice, and human patient samples, and utilize cutting-edge technologies such as multi-omics, biochemical assays, and molecular biological tools to address the questions of our interest. Guided by these mechanistic insights, we employ AI-driven virtual screening and molecular docking to design small-molecule inhibitors and therapeutic antibodies against newly identified targets, with the ultimate goal of advancing precision cancer therapy.

Ongoing projects include:

• Investigating the role of stress-induced membrane proteins in PDAC initiation and metastasis, along with the development of corresponding therapeutic strategies;

• Elucidating the molecular mechanisms by which cancer-associated fibroblasts promote PDAC progression and chemoresistance, and developing novel targeted therapeutics against these processes.

If you are interested in cancer biology and being a part of our team, please email me at wuchengsheng@ucas.ac.cn.