Kinectin1 depletion promotes EGFR degradation via the ubiquitin-proteosome system in cutaneous squamous cell carcinoma

Ma, Ji; Ma, Shudong; Zhang, Ying; Shen, Yi; Huang, Lei; Lu, Tianhao; Wang, Lu; Wen, Yunhan; Ding, Zhenhua

doi:10.1038/s41419-021-04276-5

Cited by 6 publications

(3 citation statements)

References 54 publications

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“…CCDC40 encodes a protein affecting motile cilia that participates in cell division; only 1 study has explored the role of CCDC40 in cancer. Ma et al reported that CCDC40 plays a tumor suppressor role through regulating the deubiquitination process to promote the degradation of EGFR ( 36 ). Our study also supported that CCDC40 serves as a tumor suppressor, but the effect of CCDC40 in UVM remained unexplored.…”

Section: Discussionmentioning

confidence: 99%

A centrosome-related gene signature for predicting the overall survival of uveal melanoma

Yu,

Guo,

et al. 2024

Transl Cancer Res

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Background Centrosome aberration (CA) plays a vital role in tumorigenesis and metastasis under pathophysiological conditions. The existence of CA was first reported in uveal melanoma (UVM) recently. Our study aimed to investigate the association of centrosome-related genes with UVM prognosis. Methods The Cancer Genome Atlas (TCGA)-UVM and Gene Expression Omnibus series (GSE) 22138 were included in the study. Least absolute shrinkage and selection operator (LASSO) and Cox regression were combined to screen out key genes and construct a centrosome-related gene signature. Kaplan-Meier (KM) survival curves were used to evaluate the survival differences between the 2 groups. Gene enrichment, immune infiltration, and mutation profile were used to explore the underlying mechanism. Results A centrosome-related gene signature was constructed: Risk score =−3.27071 × MAP6 − 5.03735 × CCDC40 − 2.68459 × PRKCD + 1.826349 × IGFBP4 + 11.66582 × RAB6C − 4.86899 × CCND3. The survival possibilities of the two groups were significantly different. The high-risk group showed cancer progression, inflammation, and immune restriction characteristics when compared with the low-risk group. BAP1 mutation was associated with high risk and SF3B1 mutation was associated with low risk according to the signature. Conclusions Our study first investigated the role of centrosome-related genes in UVM overall survival (OS). We then constructed a centrosome-related gene signature for UVM, which provides new insights into the role of CA in UVM and identifies novel centrosome-related biomarkers.

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Section: Discussionmentioning

confidence: 99%

A centrosome-related gene signature for predicting the overall survival of uveal melanoma

Yu,

Guo,

et al. 2024

Transl Cancer Res

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“… 44 , 45 In 2021, Zhenhua Ding and his colleagues made a breakthrough in their study on KTN1 function. They found that KTN1 stabilized the protein expression level of EGFR by decreasing its ubiquitination, 46 suggesting that the MALAT1-KTN1-EGFR axis promoted the development of cutaneous squamous cell carcinoma. 47 These results revealed that KTN1 participated in the regulation of protein degradation; hence, we focused on whether KTN1 regulates the protein expression of PRMT1.…”

Section: Discussionmentioning

confidence: 99%

PRMT1 promotes the proliferation and metastasis of gastric cancer cells by recruiting MLXIP for the transcriptional activation of the β-catenin pathway

Wang¹,

Chen²,

Peng³

et al. 2023

Genes & Diseases

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“…As one of the most clinically useful targets, EGFR has been applied as a gold standard for treating various cancer patients [ 29 – 31 ]. However, rapidly acquired resistance and limited patient range have largely restricted its clinical application.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory role of proguanil on the growth of bladder cancer via enhancing EGFR degradation and inhibiting its downstream signaling pathway to induce autophagy

Xiao

Peng

et al. 2022

Cell Death Dis

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A major reason for the high mortality of patients with bladder cancer (BC) is that chemotherapy and surgery are only effective for very limited patients. Thus, developing novel treatment options becomes an urgent need for improving clinical outcomes and the quality of life for BC patients. Here, we demonstrated that proguanil significantly inhibited the growth of BC in vitro and in vivo. Importantly, our results indicated that the sensitivity of BC cells to proguanil is positively correlated with the expression of epidermal growth factor receptor (EGFR). Mechanistically, proguanil specifically targeted EGFR and promoted EGFR binding to Caveolin-1, enhanced its endocytosis in a Clathrin-independent manner, and then recruited c-Cbl to promote EGFR ubiquitination and degradation through the lysosomal pathway. Further studies suggested that proguanil induced autophagy by destabilizing EGFR and inhibiting its downstream signaling pathway. Thus, this study reveals the novel mechanism of proguanil on anticancer activity and implies the potential benefits of this drug in the treatment of BC.

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Kinectin1 depletion promotes EGFR degradation via the ubiquitin-proteosome system in cutaneous squamous cell carcinoma

Cited by 6 publications

References 54 publications

A centrosome-related gene signature for predicting the overall survival of uveal melanoma

A centrosome-related gene signature for predicting the overall survival of uveal melanoma

PRMT1 promotes the proliferation and metastasis of gastric cancer cells by recruiting MLXIP for the transcriptional activation of the β-catenin pathway

Inhibitory role of proguanil on the growth of bladder cancer via enhancing EGFR degradation and inhibiting its downstream signaling pathway to induce autophagy

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