Crosstalk between Epidermal Growth Factor Receptors (EGFR) and integrins in resistance to EGFR tyrosine kinase inhibitors (TKIs) in solid tumors

Javadi, Samira; Zhiani, Mina; Mousavi, Mir Ali; Fathi, Mojtaba

doi:10.1016/j.ejcb.2020.151083

Cited by 29 publications

(25 citation statements)

References 128 publications

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“…The neoplasm with the largest number of patients in this study was breast cancer, which showed a significant positive correlation in PT between the T/Bp value and the molecular subtypes, with the highest T/Bp ratios for the HER2+ and Luminal B subtypes HER2+. The T/Bp values in HER2+ breast cancer showed a significant decrease in the LN metastases regarding PT (Figure 7), which may be due to crosstalking (cross-regulation), which occurs between integrins and EGFR receptors, such as HER2 [18,19]. Additionally, it is known that the Wnt signaling pathway promotes the proliferation and invasion of breast cancer cells in a HER2-dependent manner [20].…”

Section: Discussionmentioning

confidence: 98%

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

et al. 2022

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Fibroblast activation protein (FAP) is highly expressed on the cancer-associated fibroblasts (CAF) of the tumor stroma. Recently, we reported the preclinical evaluation and clinical biokinetics of a novel 99mTc-labeled FAP inhibitor radioligand ([99mTc]Tc-iFAP). This research aimed to evaluate [99mTc]Tc-iFAP for the tumor stroma imaging of six different cancerous entities and analyze them from the perspective of stromal heterogeneity. [99mTc]Tc-iFAP was prepared from freeze-dried kits with a radiochemical purity of 98 ± 1%. The study included thirty-two patients diagnosed with glioma (n = 5); adrenal cortex neuroendocrine tumor (n = 1); and breast (n = 21), lung (n = 2), colorectal (n = 1) and cervical (n = 3) cancer. Patients with glioma had been evaluated with a previous cranial MRI scan and the rest of the patients had been involved in a [18F]FDG PET/CT study. All oncological diagnoses were corroborated histopathologically. The patients underwent SPECT/CT brain imaging (glioma) or thoracoabdominal imaging 1 h after [99mTc]Tc-iFAP administration (i.v., 735 ± 63 MBq). The total lesions (n = 111) were divided into three categories: primary tumors (PT), lymph node metastases (LNm), and distant metastases (Dm). [99mTc]Tc-iFAP brain imaging was positive in four high-grade WHO III–IV gliomas and negative in one treatment-naive low-grade glioma. Both [99mTc]Tc-iFAP and [18F]FDG detected 26 (100%) PT, although the number of positive LNm and Dm was significantly higher with [18F]FDG [82 (96%)], in comparison to [99mTc]Tc-iFAP imaging (35 (41%)). Peritoneal carcinomatosis lesions in a patient with recurrent colorectal cancer were only visualized with [99mTc]Tc-iFAP. In patients with breast cancer, a significant positive correlation was demonstrated among [99mTc]Tc-iFAP uptake values (Bq/cm3) of PT and the molecular subtype, being higher for subtypes HER2+ and Luminal B HER2-enriched. Four different CAF subpopulations have previously been described for LNm of breast cancer (from CAF-S1 to CAF-S4). The only subpopulation that expresses FAP is CAF-S1, which is preferentially detected in aggressive subtypes (HER2 and triple-negative), confirming that FAP+ is a marker for poor disease prognosis. The results of this pilot clinical research show that [99mTc]Tc-iFAP SPECT imaging is a promising tool in the prognostic assessment of some solid tumors, particularly breast cancer.

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Section: Discussionmentioning

confidence: 98%

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

et al. 2022

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“…Cell surface integrins bind to the ECM and form focal adhesions, which are large multi-protein complexes that act as the link between sensing mechanical changes and intracellular signaling that promotes cell survival, migration, and proliferation ( Buchheit et al, 2014 ; Elmore, 2007 ; Paoli et al, 2013 ). Receptor tyrosine kinases, including EGFR, are major contributors to focal adhesion signaling ( Javadi et al, 2020 ). Once integrin disengagement occurs, EGFR is trafficked to the lysosome for degradation, and this terminates pro-survival signaling that would otherwise promote cell survival under detached growth conditions ( Grassian et al, 2011 ; Reginato et al, 2003 ).…”

Section: Prp4k As a Cancer Biomarker And Haploinsufficient Tumour Sup...mentioning

confidence: 99%

Tinker, Tailor, Tumour Suppressor: The Many Functions of PRP4K

2022

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Pre-mRNA processing factor 4 kinase (PRP4K, also known as PRPF4B) is an essential kinase first identified in the fission yeast Schizosaccharomyces pombe that is evolutionarily conserved from amoebae to animals. During spliceosomal assembly, PRP4K interacts with and phosphorylates PRPF6 and PRPF31 to facilitate the formation of the spliceosome B complex. However, over the past decade additional evidence has emerged that PRP4K has many diverse cellular roles beyond splicing that contribute to tumour suppression and chemotherapeutic responses in mammals. For example, PRP4K appears to play roles in regulating transcription and the spindle assembly checkpoint (SAC), a key pathway in maintaining chromosomes stability and the response of cancer cells to taxane-based chemotherapy. In addition, PRP4K has been revealed to be a haploinsufficient tumour suppressor that promotes aggressive cancer phenotypes when partially depleted. PRP4K is regulated by both the HER2 and estrogen receptor, and its partial loss increases resistance to the taxanes in multiple malignancies including cervical, breast and ovarian cancer. Moreover, ovarian and triple negative breast cancer patients harboring tumours with low PRP4K expression exhibit worse overall survival. The depletion of PRP4K also enhances both Yap and epidermal growth factor receptor (EGFR) signaling, the latter promoting anoikis resistance in breast and ovarian cancer. Finally, PRP4K is negatively regulated during epithelial-to-mesenchymal transition (EMT), a process that promotes increased cell motility, drug resistance and cancer metastasis. Thus, as we discuss in this review, PRP4K likely plays evolutionarily conserved roles not only in splicing but in a number of cellular pathways that together contribute to tumour suppression.

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“…Blockade of the STAT3 signaling pathway may induce apoptosis and has been shown to eradicate tumor-initiating cells related to prostate cancer [ 129 , 130 ]. EGF interaction with EGFR has also been shown to involve crosstalk with integrin αvβ3 [ 87 , 88 ].…”

Section: The Interactions Between Carcinogenic Effectors and Heteroneminmentioning

confidence: 99%

The power of heteronemin in cancers

et al. 2022

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Heteronemin (Haimian jing) is a sesterterpenoid-type natural marine product that is isolated from sponges and has anticancer properties. It inhibits cancer cell proliferation via different mechanisms, such as reactive oxygen species (ROS) production, cell cycle arrest, apoptosis as well as proliferative gene changes in various types of cancers. Recently, the novel structure and bioactivity evaluation of heteronemin has received extensive attention. Hormones control physiological activities regularly, however, they may also affect several abnormalities such as cancer. L-Thyroxine (T4), steroid hormones, and epidermal growth factor (EGF) up-regulate the accumulation of checkpoint programmed death-ligand 1 (PD-L1) and promote inflammation in cancer cells. Heteronemin suppresses PD-L1 expression and reduces the PD-L1-induced proliferative effect. In the current review, we evaluated research and evidence regarding the antitumor effects of heteronemin and the antagonizing effects of non-peptide hormones and growth factors on heteronemin-induced anti-cancer properties and utilized computational molecular modeling to explain how these ligands interacted with the integrin αvβ3 receptors. On the other hand, thyroid hormone deaminated analogue, tetraiodothyroacetic acid (tetrac), modulates signal pathways and inhibits cancer growth and metastasis. The combination of heteronemin and tetrac derivatives has been demonstrated to compensate for anti-proliferation in cancer cells under different circumstances. Overall, this review outlines the potential of heteronemin in managing different types of cancers that may lead to its clinical development as an anticancer agent.

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Crosstalk between Epidermal Growth Factor Receptors (EGFR) and integrins in resistance to EGFR tyrosine kinase inhibitors (TKIs) in solid tumors

Cited by 29 publications

References 128 publications

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

[99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

Tinker, Tailor, Tumour Suppressor: The Many Functions of PRP4K

The power of heteronemin in cancers

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