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

Guo, Zhiyong; Ashrafizadeh, Milad; Zhang, Wei; Zou, Rongjun; Sethi, Gautam; Zhang, Xianbin

doi:10.1007/s10555-023-10125-y

Cited by 18 publications

(7 citation statements)

References 317 publications

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“…As mentioned, hypoxia is involved in EMT induction and facilitated cancer invasion which can be overcome by β-patchoulene [ 57 ]. Moreover, there is a close association between EMT induction and drug resistance in human cancers [ 58 ]. Noteworthy, inhibition of Wnt/β-catenin by fucoxanthin can suppress EMT in lung cancer, suggesting the role of Wnt as a regulator of EMT [ 59 ] (will be discussed in details in next sections).…”

Section: Emt Mechanism: General Aspects and Carcinogenic Functionmentioning

confidence: 99%

Wnt/β-catenin-driven EMT regulation in human cancers

Xue,

Yang,

Chen

et al. 2024

Cell. Mol. Life Sci.

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Metastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial–mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/β-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3β that destructs β-catenin, while ligand–receptor interaction impairs GSK-3β function to increase β-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/β-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance β-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/β-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/β-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression. Graphical abstract

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Section: Emt Mechanism: General Aspects and Carcinogenic Functionmentioning

confidence: 99%

Wnt/β-catenin-driven EMT regulation in human cancers

Xue,

Yang,

Chen

et al. 2024

Cell. Mol. Life Sci.

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“…Despite the valuable functions of EMT during the physiological and developmental stages, the function of EMT in cancer is oncogenic. Although EMT has been confirmed as a modulator of cancer migration, the increasing evidences have shown that EMT can also mediate the drug resistance [ 21 , 22 ]. Therefore, the recent experiments have emphasized on highlighting the underlying mechanisms modulating EMT in human cancers.…”

Section: The Function Of Emt In Tumorigenesismentioning

confidence: 99%

Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance

Ashrafizadeh,

Dai,

Torabian

et al. 2024

Cell. Mol. Life Sci.

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The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.

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“…Last but not least, the PDAC tumor microenvironment is highly immunosuppressive and desmoplastic, facilitating tumor growth, invasion, and metastasis while impeding immune surveillance and therapeutic response. Stromal interactions and extracellular matrix remodeling further enhance tumor aggressiveness and therapeutic resistance (175)(176)(177).…”

Section: Mirnas In Pdacmentioning

confidence: 99%

The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers

Jafari,

Motedayyen,

Javadi

et al. 2024

Front. Oncol.

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Pancreatic ductal adenocarcinoma (PDAC) is among the most penetrative malignancies affecting humans, with mounting incidence prevalence worldwide. This cancer is usually not diagnosed in the early stages. There is also no effective therapy against PDAC, and most patients have chemo-resistance. The combination of these factors causes PDAC to have a poor prognosis, and often patients do not live longer than six months. Because of the failure of conventional therapies, the identification of key biomarkers is crucial in the early diagnosis, treatment, and prognosis of pancreatic cancer. 65% of the human genome encodes ncRNAs. There are different types of ncRNAs that are classified based on their sequence lengths and functions. They play a vital role in replication, transcription, translation, and epigenetic regulation. They also participate in some cellular processes, such as proliferation, differentiation, metabolism, and apoptosis. The roles of ncRNAs as tumor suppressors or oncogenes in the growth of tumors in a variety of tissues, including the pancreas, have been demonstrated in several studies. This study discusses the key roles of some lncRNAs and miRNAs in the growth and advancement of pancreatic carcinoma. Because they are involved not only in the premature identification, chemo-resistance and prognostication, also their roles as potential biomarkers for better management of PDAC patients.

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

Cited by 18 publications

References 317 publications

Wnt/β-catenin-driven EMT regulation in human cancers

Wnt/β-catenin-driven EMT regulation in human cancers

Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance

The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers

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