EGFR-Dependent Extracellular Matrix Protein Interactions Might Light a Candle in Cell Behavior of Non-Small Cell Lung Cancer

Abdel-Mawgood, Ahmed L.; Ibrahim, Sherif

doi:10.3389/fonc.2021.766659

Cited by 16 publications

(9 citation statements)

References 215 publications

(268 reference statements)

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“…In this study, we examined functional roles of PTK2 in lung cancer progression via the cross-talk between EGFR-and TLRs-mediated signaling, which has been considered as critical therapeutic targets for the intervention of lung cancer diseases [3][4][5][6][7][8][9]. We found that the survival of NSCLC patients with up-regulated PTK2 was critically lower than that of TLRs-mediated signaling is essentially implicated in lung cancer progression [3][4][5][6][7][8][9][10][11][12], the ability of cancer progression was significantly enhanced in response to EGF, Pam3csk4 (an agonist of TLR1/2), and FSL-1…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, EGFR as a receptor tyrosine kinase belonging to the ErbB family of proteins can critically affect the proliferation, angiogenesis, migration, invasion, and tumorigenicity in lung cancer [11,12]. These results strongly provide theoretical possibility for the development of therapies that target EGFR and TLR signaling pathways for the treatment of lung cancer.…”

Section: Introductionmentioning

confidence: 90%

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PTK2 promotes lung cancer progression via cross-talk regulation between EGFR- and TLR-mediated signaling

Kim,

Shin,

Kim

et al. 2024

Preprint

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Introduction Protein tyrosine kinase 2 (PTK2) plays a pivotal role in various cancers via cross-talk with growth factor signaling pathways. PTK2 is amplified in non-small cell lung cancer (NSCLC). However, the functional role of PTK2 has not been elucidated yet. Here, we report that PTK2 is functionally implicated in epidermal growth factor receptor (EGFR)- and toll-like receptors (TLRs)-mediated signaling for progression of lung cancer. Methods Microarray data of NSCLC tumor tissues and matched normal tissues of 42 NSCLC patients were used to gain insights into associations of PTK2 and EGFR expression with patient’s prognosis and cancer progression. CRISPR-Cas9 gene editing method and cancer progression assay were utilized for functional validation of PTK2 in human A549 and H1299 lung cancer cells. In vitro and in vivo tumorigenic assays were performed using a three-dimensional (3D) tumor spheroid formation and a xenografted NOD scid gamma mouse (NSG, NOD/SCID/IL-2Rγnull) model, respectively. Results Patients with up-regulated PTK2 exhibited a poor prognosis after clinical treatments. Gene set enrichment assay (GSEA) revealed that patients with up-regulated PTK2 exhibited high enrichments of gene sets related to lung cancer progression and EGFR- or TLRs-mediated signaling. The functional association between PTK2 and EGFR or TLRs was verified. PTK2-knockout (KO) lung cancer cells exhibited marked attenuations of cancer progression, and in vivo tumorigenic and metastatic activity in xenografted NSG mice. In response to TLR agonists, EGF, or TLR agonists plus EGF, the severe decreases of 3D-tumor spheroid formation could be observed in PTK2-KO lung cancer cells. We further elucidated the molecular mechanism by which PTK2 regulated the cross-talk between EGFR- and TLRs-mediated signaling. PTK2 specifically regulated their downstream molecules for the activation of NF-κB. Conclusions Up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients. It could be potentially considered as a therapeutic target in the field of precision or personalized cancer medicine aiming for NSCLC intervention.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

PTK2 promotes lung cancer progression via cross-talk regulation between EGFR- and TLR-mediated signaling

Kim,

Shin,

Kim

et al. 2024

Preprint

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“…Although NSCLC progression depends on driver mutations, it is also affected by the extracellular matrix interaction which is mediated by integrins [37,38]. Integrins are cell adhesions and play a key role in the regulation of the process of tumor angiogenesis, which consists of basement membrane degradation and endothelial cell migration, proliferation, and stabilization [39,40].…”

Section: Discussionmentioning

confidence: 99%

Different Tyrosine Kinase Inhibitors Used in Treating EGFR-Mutant Pulmonary Adenocarcinoma with Brain Metastasis and Intracranial Intervention Have No Impact on Clinical Outcomes

Kuo

Tsai

Hung

et al. 2022

Cancers

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Brain metastasis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is a factor of poor prognosis. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. A total of 186 patients treated with an EGFR TKI were enrolled in the study, and 79 (42%) received intracranial intervention. Patients who received intracranial intervention and those who did not had a similar treatment response rate (RR), progression-free survival (PFS) (median PFS: 11.0 vs. 10.0 months, p = 0.4842), and overall survival (OS) (median OS: 23.0 vs. 23.2 months, p = 0.2484). Patients treated with gefitinib, erlotinib, afatinib, or osimertinib had a similar RR (63%, 76%, 81%, or 100%, respectively, p = 0.1390), but they had significantly different PFS (median PFS: 7.5, 10.0, 14.8 months, or not reached, respectively, p = 0.0081). In addition, OS tended to be different between different EGFR TKI treatments (median OS of 19.2, 23.7, or 33.0 months for gefitinib, erlotinib, or afatinib treatments, respectively, p = 0.0834). Afatinib and osimertinib both demonstrated significantly longer PFS than gefitinib in a Cox regression model. Graded prognostic assessment (GPA) versions 2017 and 2022 stratified patients with different OS; patients with higher GPA index scores had significantly longer OS (p = 0.0368 and 0.0407 for version 2017 and 2022, respectively).

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“…Sun et al, 2022). In fact, crosstalk has been identified as a major avenue for both disease progression and therapy resistance in cancer (Hassanein et al, 2021; Lai et al, 2018). Unfortunately, nearly every type of cancer benefits from receptor signaling crosstalk as a mechanism to amplify uncontrolled cellular proliferation, adhesion‐independent survival, and metastatic invasion and migration.…”

Section: Contribution Of Receptor Crosstalk Dysregulation In Diseasementioning

confidence: 99%

How cells sense and integrate information from different sources

Ullo

Case

2023

WIREs Mechanisms of Disease

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Cell signaling is a fundamental cellular process that enables cells to sense and respond to information in their surroundings. At the molecular level, signaling is primarily carried out by transmembrane protein receptors that can initiate complex downstream signal transduction cascades to alter cellular behavior. In the human body, different cells can be exposed to a wide variety of environmental conditions, and cells express diverse classes of receptors capable of sensing and integrating different signals. Furthermore, different receptors and signaling pathways can crosstalk with each other to calibrate the cellular response. Crosstalk occurs through multiple mechanisms at different levels of signaling pathways. In this review, we discuss how cells sense and integrate different chemical, mechanical, and spatial signals as well as the mechanisms of crosstalk between pathways.To illustrate these concepts, we use a few well-studied signaling pathways, including receptor tyrosine kinases and integrin receptors. Finally, we discuss the implications of dysregulated cellular sensing on driving diseases such as cancer.

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EGFR-Dependent Extracellular Matrix Protein Interactions Might Light a Candle in Cell Behavior of Non-Small Cell Lung Cancer

Cited by 16 publications

References 215 publications

PTK2 promotes lung cancer progression via cross-talk regulation between EGFR- and TLR-mediated signaling

PTK2 promotes lung cancer progression via cross-talk regulation between EGFR- and TLR-mediated signaling

Different Tyrosine Kinase Inhibitors Used in Treating EGFR-Mutant Pulmonary Adenocarcinoma with Brain Metastasis and Intracranial Intervention Have No Impact on Clinical Outcomes

How cells sense and integrate information from different sources

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