Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges

Butti, Ramesh; Das, Sumit; Gunasekaran, Vinoth Prasanna; Yadav, Amit Singh; Kumar, Dhiraj; Kundu, Gopal C.

doi:10.1186/s12943-018-0797-x

Cited by 273 publications

(190 citation statements)

References 183 publications

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“…Altered EGFR-family RTK signalling is most commonly associated with the induction of aggressive tumour characteristics, such as invasion, proliferation or angiogenesis in breast tumours (Butti, Das et al, 2018, Masuda, Zhang et al, 2012. To complement the picture, our data shows that ISG15 expression and prognosis are inversely associated in patients with lymph nodes metastasis ( Fig.1B-C) with the highest association in the Luminal B and basal-like subtype (Fig.S1A).…”

Section: Discussionmentioning

confidence: 69%

ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling

Bolado-Carrancio

Muir

Ewing

et al. 2019

Preprint

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ISG15 is an ubiquitin-like modifier that is associated with reduced survival rates in breast cancer patients. However, the mechanism by which ISG15 achieves this remains elusive.We demonstrate that modification of Rab GDP-Dissociation Inhibitor Beta (GDI2) by ISG15 (ISGylation) alters endocytic recycling of the EGF receptor (EGFR). By regulating EGFR trafficking, ISGylation sustains Akt-signalling in vitro and in vivo. Persistent and enhanced Akt activation explains the more aggressive tumour behaviour observed in animal models and human breast cancers. We show that ISGylation can act as driver of tumour progression rather than merely being a marker of it.

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Section: Discussionmentioning

confidence: 69%

ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling

Bolado-Carrancio

Muir

Ewing

et al. 2019

Preprint

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“…Furthermore, breast cancer patients with high levels of IL-6 compared to the heathy control groups indicate cachexia symptoms and are characterized by weight loss (33,57,58). Additionally, the activation of JAK/STAT, PI3K, and MAPK pathways linked to cancer metastasis, tumor cell proliferation, differentiation, apoptosis, angiogenesis and invasion have been identifi ed in patients with breast cancer (59)(60)(61)(62). In our study, the expression levels of IL-6 and STAT-3 were signifi cantly higher in cachectic and non-cachectic breast cancer patients than that of the control group, and especially these mRNA levels were up-regulated in breast cancer with cachexia.…”

Section: Discussionmentioning

confidence: 99%

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

Eskiler¹,

Bezdegümeli²,

Özman³

et al. 2019

BLL

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OBJECTIVES: We investigated the changes in the IL-6 and STAT3 expression levels in cachectic and noncachectic patients with gastric, lung and breast cancer and evaluated the association between IL-6 and STAT3 levels and cancer types in terms of cachexia condition. BACKGROUND: Cancer-associated cachexia, observed in nearly 50-80 % of cancer patients, has drawn attention in advanced patients. IL-6/JAK/STAT pathway plays an essential role in the progression of cancer cachexia through the regulation of the infl ammatory response. METHODS: This study consisted of 48 gastric, breast and lung cancer patients (18 cachectic and 30 noncachectic) and healthy individuals. Total RNA isolation and cDNA synthesis was performed after the collection of blood samples. IL-6 and STAT3 expression levels were analyzed by RT-PCR analysis. RESULTS: Our fi ndings demonstrated that IL-6 mRNA levels considerably increased 19.89 ± 8.25, 5.18 ± 2.81 and 15.33±9.54-fold in gastric, lung and breast cancer patients with cachexia, respectively. Additionally, a 16.67±7.13, 14.21 ± 11.72 and 8.85 ± 3.89-fold increase in the STAT3 expression level was detected in cachectic gastric, lung and breast cancer patients, respectively (p < 0.01). CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62).

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“…Subsequently, the RTK pathway was activated by ACE2. RTKs can be expressed in many cell types, including cells in the tumor microenvironment [26]. As a key regulator of cancer development, the RTK pathway plays an important role in the proliferation, invasion, angiogenesis, and metastasis of cancer [27].…”

Section: Discussionmentioning

confidence: 99%

The potential effect of the angiotensin-converting enzyme 2 (ACE2) receptor of 2019-nCoV on lung adenocarcinoma patients

Huo¹,

Li²,

Shao³

et al. 2020

Preprint

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BackgroundThe 2019-nCoV epidemic is the public health emergency that has had the greatest impact on the world. Our study aimed to better understand the underlying mechanisms and function of angiotensin-converting enzyme 2 (ACE2) receptor of 2019-nCoV on lung adenocarcinoma patients (LUAD), and provide a theoretical basis for early diagnosis, prognosis and targeted therapy of 2019-nCoV. MethodsThis study focuses on the expression level, functions, mutation rate, and copy number variations (CNVs) of ACE2 in LUAD using an extensive bioinformatics data mining process. The interaction between ACE2 expression and clinical-pathological parameters of patients with LUAD was investigated using UALCAN. Also, the essential biological features, single nucleotide variations (SNVs), CNVs, and pathway activities of genes interacting with ACE2 in these cancers were further analyzed. ResultsWe found that ACE2 expression in LUAD patients increased with age, but it was not related to cancer status, patient’s race, patient’s gender, or patient’s smoking habits. Moreover, our results showed that compared to that in normal tissues, ACE2 was highly expressed in colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), and stomach adenocarcinoma (STAD). However, there is no significant difference in the expression of ACE2 in patients of different ages. ConclusionsThese findings demonstrate the importance of ACE2 in LUAD, and provide insights into the regulatory mechanisms and function of ACE2.

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Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges

Cited by 273 publications

References 183 publications

ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling

ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

The potential effect of the angiotensin-converting enzyme 2 (ACE2) receptor of 2019-nCoV on lung adenocarcinoma patients

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