Knockdown of ADAM17 inhibits cell proliferation and increases oxaliplatin sensitivity in HCT-8 colorectal cancer through EGFR-PI3K-AKT activation

Zhang, Qi; Wang, Changyou; Han, Xuechao; Yang, Guanghua; Ge, Zhipeng; Zhang, Guozhi

doi:10.1016/j.bbrc.2018.06.158

Cited by 14 publications

(8 citation statements)

References 21 publications

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“…Chemotherapy activates ADAM17 expression, leading to growth factor shedding, growth factor receptor activation, and drug resistance in CRC [144]. Pharmacological inhibition or siRNA silencing of ADAM17 activity, combined with chemotherapy, has potential therapeutic benefits for CRC patients [144][145][146][147][148][149]. Wang et al [150] suggested that Nox1 promoted CRC metastasis through the regulation of ADAM17 stability.…”

Section: Adammentioning

confidence: 99%

Extracellular Matrix Biomarkers in Colorectal Cancer

Kim

et al. 2021

IJMS

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The cellular microenvironment composition and changes therein play an extremely important role in cancer development. Changes in the extracellular matrix (ECM), which constitutes a majority of the tumor stroma, significantly contribute to the development of the tumor microenvironment. These alterations within the ECM and formation of the tumor microenvironment ultimately lead to tumor development, invasion, and metastasis. The ECM is composed of various molecules such as collagen, elastin, laminin, fibronectin, and the MMPs that cleave these protein fibers and play a central role in tissue remodeling. When healthy cells undergo an insult like DNA damage and become cancerous, if the ECM does not support these neoplastic cells, further development, invasion, and metastasis fail to occur. Therefore, ECM-related cancer research is indispensable, and ECM components can be useful biomarkers as well as therapeutic targets. Colorectal cancer specifically, is also affected by the ECM and many studies have been conducted to unravel the complex association between the two. Here we summarize the importance of several ECM components in colorectal cancer as well as their potential roles as biomarkers.

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Section: Adammentioning

confidence: 99%

Extracellular Matrix Biomarkers in Colorectal Cancer

Kim

et al. 2021

IJMS

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“…Specifically, ADAM17 is known to have a major role in activating most ligands of EGFR, such as amphiregulin, heparin-binding epidermal growth factor and epigen, representing a crucial pathway for tumor progression [ 12 ]. In colorectal cancer, the downregulation of ADAM17 could increase the sensitivity to chemotherapy, inhibit cell proliferation, induce apoptosis, and reverse oxaliplatin resistance via suppression of the EGFR/PI3K/AKT signaling pathway [ 13 ]. Notably, RA was reported to inhibit head and neck squamous cell carcinoma in vitro through a reduction in EGFR activation [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Rosmarinic acid inhibits proliferation and migration, promotes apoptosis and enhances cisplatin sensitivity of melanoma cells through inhibiting ADAM17/EGFR/AKT/GSK3β axis

et al. 2021

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“…However, the role played by glycosylation LAMC1 was not mentioned in previous studies. ADA17 (ADAM17) at the protein level was reported to induce drug resistance through hypoxia through PI3K/Akt pathway ( Wang et al, 2013 ; Zhang et al, 2018 ). For SIRBL (SIRPB1), there was no direct study reported that it played a role in drug resistance, it was indeed found to promote cell proliferation via Akt activation( Song et al, 2020 ), which was evidence of drug resistance, since cancer cells normally become more malignant with the higher capability of proliferation, migration, etc.…”

Section: Discussionmentioning

confidence: 99%

Investigation on acquired palbociclib resistance by LC-MS based multi-omics analysis

Xue

Zeng²,

Yin³

et al. 2023

Front. Mol. Biosci.

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Palbociclib is a specific CDK4/6 inhibitor that has been widely applied in multiple types of tumors. Different from cytotoxic drugs, the anticancer mechanism of palbociclib mainly depends on cell cycle inhibition. Therefore, the resistance mechanism is different. For clinical cancer patients, drug resistance is inevitable for almost all cancer therapies including palbociclib. We have trained palbociclib resistant cells in vitro to simulate the clinical situation and applied LC-MS multi-omics analysis methods including proteomic, metabolomic, and glycoproteomic techniques, to deeply understand the underly mechanism behind the resistance. As a result of proteomic analysis, the resistant cells were found to rely on altered metabolic pathways to keep proliferation. Metabolic processes related to carbohydrates, lipids, DNA, cellular proteins, glucose, and amino acids were observed to be upregulated. Most dramatically, the protein expressions of COX-1 and NDUFB8 have been detected to be significantly overexpressed by proteomic analysis. When a COX-1 inhibitor was hired to combine with palbociclib, a synergistic effect could be obtained, suggesting the altered COX-1 involved metabolic pathway is an important reason for the acquired palbociclib resistance. The KEGG pathway of N-glycan biosynthesis was identified through metabolomics analysis. N-glycoproteomic analysis was therefore included and the global glycosylation was found to be elevated in the palbociclib-resistant cells. Moreover, integration analysis of glycoproteomic data allowed us to detect a lot more proteins that have been glycosylated with low abundances, these proteins were considered to be overwhelmed by those highly abundant proteins during regular proteomic LC-MS detection. These low-abundant proteins are mainly involved in the cellular biology processes of cell migration, the regulation of chemotaxis, as well as the glycoprotein metabolic process which offered us great more details on the roles played by N-glycosylation in drug resistance. Our result also verified that N-glycosylation inhibitors could enhance the cell growth inhibition of palbociclib in resistant cells. The high efficiency of the integrated multi-omics analysis workflow in discovering drug resistance mechanisms paves a new way for drug development. With a clear understanding of the resistance mechanism, new drug targets and drug combinations could be designed to resensitize the resistant tumors.

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Knockdown of ADAM17 inhibits cell proliferation and increases oxaliplatin sensitivity in HCT-8 colorectal cancer through EGFR-PI3K-AKT activation

Cited by 14 publications

References 21 publications

Extracellular Matrix Biomarkers in Colorectal Cancer

Extracellular Matrix Biomarkers in Colorectal Cancer

Rosmarinic acid inhibits proliferation and migration, promotes apoptosis and enhances cisplatin sensitivity of melanoma cells through inhibiting ADAM17/EGFR/AKT/GSK3β axis

Investigation on acquired palbociclib resistance by LC-MS based multi-omics analysis

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