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Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance

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Abstract

The metastasis is a multistep process in which a small proportion of cancer cells are detached from the colony to enter into blood cells for obtaining a new place for metastasis and proliferation. The metastasis and cell plasticity are considered major causes of cancer-related deaths since they improve the malignancy of cancer cells and provide poor prognosis for patients. Furthermore, enhancement in the aggressiveness of cancer cells has been related to the development of drug resistance. Metastasis of pancreatic cancer (PC) cells has been considered one of the major causes of death in patients and their undesirable prognosis. PC is among the most malignant tumors of the gastrointestinal tract and in addition to lifestyle, smoking, and other factors, genomic changes play a key role in its progression. The stimulation of EMT in PC cells occurs as a result of changes in molecular interaction, and in addition to increasing metastasis, EMT participates in the development of chemoresistance. The epithelial, mesenchymal, and acinar cell plasticity can occur and determines the progression of PC. The major molecular pathways including STAT3, PTEN, PI3K/Akt, and Wnt participate in regulating the metastasis of PC cells. The communication in tumor microenvironment can provide by exosomes in determining PC metastasis. The components of tumor microenvironment including macrophages, neutrophils, and cancer-associated fibroblasts can modulate PC progression and the response of cancer cells to chemotherapy.

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Authors and Affiliations

  1. Department of Oncology, First Affiliated Hospital, Gannan Medical University, 128 Jinling Road, Ganzhou City, Jiangxi Province, 341000, China

    Zhenli Guo

  2. Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055, Guangdong, China

    Milad Ashrafizadeh, Wei Zhang & Xianbin Zhang

  3. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Milad Ashrafizadeh

  4. Department of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, Guangdong, China

    Rongjun Zou

  5. The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China

    Rongjun Zou

  6. Department of Pharmacology, National University of Singapore, 16 Medical Drive, Singapore, 117600, Singapore

    Gautam Sethi

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Zhenli Guo, Milad Ashrafizadeh, Wei Zhang, and Rongjun Zou wrote the first draft of the manuscript. Gautam Sethi and Xianbin Zhang developed the concept, collected papers, and performed English Editing.

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Guo, Z., Ashrafizadeh, M., Zhang, W. et al. Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance. Cancer Metastasis Rev 43, 29–53 (2024). https://doi.org/10.1007/s10555-023-10125-y

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