Analysis of a cytoskeleton-associated kinase PEAK1 and E-cadherin in gastric cancer

Guo, Qingqu; Qin, Wenjie; Li, Baozhong; Yang, Haijun; Guan, Jianyun; Liu, Zhiqiang; Li, Shoumiao

doi:10.1016/j.prp.2014.09.013

Cited by 14 publications

(14 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PEAK1 is upregulated in multiple human malignancies and has been associated with tumor invasion and metastasis [3,4]. However, PEAK1 was downexpressed in gastric cancers, higher PEAK1 expression was related with non-lymph node metastases and good prognosis [10]. Here we found that PEAK1 overexpression was related with larger tumor size, higher tumor stage, tumor grade, T stage, LN metastasis and recurrence, suggesting that PEAK1 overexpression might promote the malignant potential of breast cancer.…”

Section: Discussionmentioning

confidence: 50%

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

wang

Yan

WANG

2021

Preprint

View full text Add to dashboard Cite

Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

show abstract

Section: Discussionmentioning

confidence: 50%

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

wang

Yan

WANG

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Guo et al . reported a decrease in SgK269 expression in gastric cancer and demonstrated that loss of SgK269 is associated with tumour growth and invasion. More recently, Ding et al .…”

Section: Peak Family: Expression In Cancer and Mutationsmentioning

confidence: 95%

“…It is interesting to note that even though the majority of these studies indicate a strong link between elevated expression levels of SgK269 and SgK223 and tumour progression, a few recent studies have reported the opposite. Guo et al [44] reported downregulation of SgK269 in colorectal cancer, while its overexpression resulted in suppression of cell growth and metastasis, suggesting a role as a tumour suppressor. These studies suggest that the effects of SgK269 (and more broadly PEAK family proteins) on signalling outcomes are context dependent and may be either oncogenic or tumour suppressive depending on the type of cancer and the stage of its progression.…”

Section: Peak Family: Expression In Cancer and Mutationsmentioning

confidence: 99%

The PEAK family of pseudokinases, their role in cell signalling and cancer

et al. 2019

View full text Add to dashboard Cite

The study of pseudokinases has uncovered that catalysis-independent functions play a critical role in cell signalling regulation. However, how pseudokinases dynamically assemble and regulate oncogenic signalling pathways remains, in most cases, unclear due to a limited knowledge of the structural determinants that are critical for their functions. Here, we review the recent progress made to unravel the role of the PEAK family of pseudokinases, which comprises SgK269, SgK223 and the recently identified PEAK3, in assembling specific oncogenic signalling pathways that contribute to the progression of several aggressive cancers. We focus on recent structural advances revealing that SgK269 and SgK223 can homo-and heteroassociate via a unique dimerisation domain, comprising conserved regulatory helices directly surrounding the pseudokinase domain, which is also conserved in PEAK3. We also highlight a potential oligomerisation mechanism driven by the pseudokinase domain. While it is likely that homo-or heterodimerisation and oligomerisation mechanisms contribute to the assembly of complex signalling hubs and provide a means to spatially and temporally modulate and diversify signalling outputs, the exact role that these oncogenic scaffolds play in regulating cell migration, invasion and morphology remains unclear. Here, we attempt to link their structural characteristics to their cellular functions by providing a thorough analysis of the signalling transduction pathways they are known to modulate.

show abstract

“…The variant had not been described in the ClinVar or COSMIC databases. However, numerous studies have reported the involvement of PEAK1 in tumorigenesis [41][42][43][44][45].…”

Section: Patientmentioning

confidence: 99%

Mutation profiling in eight cases of vagal paragangliomas

et al. 2020

View full text Add to dashboard Cite

Background Vagal paragangliomas (VPGLs) belong to a group of rare head and neck neuroendocrine tumors. VPGLs arise from the vagus nerve and are less common than carotid paragangliomas. Both diagnostics and therapy of the tumors raise significant challenges. Besides, the genetic and molecular mechanisms behind VPGL pathogenesis are poorly understood. Methods The collection of VPGLs obtained from 8 patients of Russian population was used in the study. Exome library preparation and high-throughput sequencing of VPGLs were performed using an Illumina technology. Results Based on exome analysis, we identified pathogenic/likely pathogenic variants of the SDHx genes, frequently mutated in paragangliomas/pheochromocytomas. SDHB variants were found in three patients, whereas SDHD was mutated in two cases. Moreover, likely pathogenic missense variants were also detected in SDHAF3 and SDHAF4 genes encoding for assembly factors for the succinate dehydrogenase (SDH) complex. In a patient, we found a novel variant of the IDH2 gene that was predicted as pathogenic by a series of algorithms used (such as SIFT, PolyPhen2, FATHMM, MutationTaster, and LRT). Additionally, pathogenic/likely pathogenic variants were determined for several genes, including novel genes and some genes previously reported as associated with different types of tumors. Conclusions Results indicate a high heterogeneity among VPGLs, however, it seems that driver events in most cases are associated with mutations in the SDHx genes and SDH assembly factor-coding genes that lead to disruptions in the SDH complex.

show abstract

Analysis of a cytoskeleton-associated kinase PEAK1 and E-cadherin in gastric cancer

Cited by 14 publications

References 23 publications

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

The PEAK family of pseudokinases, their role in cell signalling and cancer

Mutation profiling in eight cases of vagal paragangliomas

Contact Info

Product

Resources

About