Translation initiation in colorectal cancer

Parsyan, Armen; Hernández, Greco; Meterissian, Sarkis

doi:10.1007/s10555-012-9349-9

Cited by 12 publications

(16 citation statements)

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“…Deregulation at this step of the translation process leads to abnormal gene expression, which in turn alters cell growth and possibly leads to cancer development (1)(2)(3). Translational initiation comprises a series of discrete steps and starts with the dissociation of 80S ribosomes into subunits.…”

mentioning

confidence: 99%

Paip1, an Effective Stimulator of Translation Initiation, Is Targeted by WWP2 for Ubiquitination and Degradation

Zhang

Gao

2014

Molecular and Cellular Biology

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mentioning

confidence: 99%

Paip1, an Effective Stimulator of Translation Initiation, Is Targeted by WWP2 for Ubiquitination and Degradation

Zhang

Gao

2014

Molecular and Cellular Biology

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“…It is only recently that a rapid-growing focus has been shifted to translational control in tumor development and progression of colon cancer [27]. Among the multiple steps of protein synthesis, deregulation at translation initiation level appears to play a vital role in tumor formation and metastasis [2]. As a crucial translational effector, the initiation factor eIF4E is a rate-limiting member of the eIF4F translation initiation complex, which controls the translation of various malignancy-associated mRNAs owning lengthy, highly structured 5′ UTRs [17,28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Though a substantial decrease in mortality and early treatment have happened in CRC due to the targeted screening programs, therapeutic strategies for CRC still require improvement [2]. Further study involving the molecular mechanism of malignancy may provide a novel treatment strategy for improving prognosis of CRC patients.…”

Section: Introductionmentioning

confidence: 99%

Integrin β6 can be translationally regulated by eukaryotic initiation factor 4E: Contributing to colonic tumor malignancy

et al. 2015

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It is well known that both eukaryotic initiation factor 4E (eIF4E) and integrin αvβ6 can contribute to malignant behavior of colon cancer. We have found that integrin αvβ6 and eIF4E were co-expressed and positively correlated in colon cancer tissues. Recently, deregulation of the protein synthesis apparatus has begun to gain attention as a major participant in cancer development and progression. However, the regulation of integrin β6 expression at translational level has never been investigated before. In present study, gene-silencing technique for eIF4E by small interfering RNA (siRNA) was used in all the subsequent experiments, in order to investigate whether eIF4E could translationally regulate expression of integrin β6 in colon cancer SW480 and HT-29 cell lines. Additionally, the subsequent effects of eIF4E knockdown on cellular malignant behavior were observed. siRNA in SW480 and HT-29 transfectants. Subsequently, protein expression of β6 was markedly suppressed, while mRNA expression of β6 showed no significant variation before and after eIF4E RNA interfering. Therefore, it could be seen that eIF4E could upregulate the expression of β6, without effect on β6 mRNA expression. More importantly, after treated with eIF4E siRNA, cellular migratory capacity on fibronectin of HT-29 and β6-transfected SW480 as well as their survival to 5-FU was decreased distinctly. Expression of integrin β6 could be translationally regulated by eIF4E, which subsequently contributed to tumor malignancy through enhancing cellular migration, survival, anti-apoptosis, and chemoresistance of colon cancer in vitro. Thus, targeting eIF4E in integrin αvβ6 expressing tumors can be a potential therapeutic strategy for patients with colon cancer.

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“…The mechanism involves the ability of integrins to activate the PI-3 K/Akt/mTOR and Ras-ERK-MNK pathway, which subsequently enhance eIF4E function through the inhibition of 4E-BP1 [16-18,26] and phosphorylation of eIF4E at ser209 by MNK [27]. Released eIF4E, accompanied with eIF4G and eIF4A, is then able to engage and activate eIF4F complex, leading to translation initiation of genes associated with malignancy.…”

Section: Discussionmentioning

confidence: 99%

Protein expression of eIF4E and integrin αvβ6 in colon cancer can predict clinical significance, reveal their correlation and imply possible mechanism of interaction

et al. 2014

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BackgroundBoth eukaryotic translation initiation factor 4E (eIF4E) and integrin αvβ6 play an important role in the development and progression of cancer. The aim of this study was to investigate the expression of eIF4E and Integrin αvβ6, their clinical significance as well as the two proteins’ correlation in colonic carcinoma tissues.ResultsThe expression levels of eIF4E and integrin αvβ6 were analyzed in colon cancerous and paraneoplastic tissues of 138 cases via tissue microarray (TMA)- immunohistochemistry. And their clinical significance as well as the two proteins’ correlation was also investigated. The expression of eIF4E was significantly associated with clinical TNM stage (P = 0.009), while T stage (P = 0.011) and TNM stage (P = 0.012) were significantly associated with integrin αvβ6 expression. Moderately weak correlation exists between the two proteins (r =0.299, P <0.001). The survival analysis by Kaplan-Meier and Cox regression model showed that protein expression of high eIF4E and positive integrin αvβ6, as independent prognostic factors (RR = 2.417, P = 0.001 and RR = 2.393, P = 0.001), tended to have a significantly poorer 5-year survival rate (P = 0.013 and 0.025, respectively, the log-rank test).ConclusioneIF4E and Integrin αvβ6 were indicators of tumor’s progression and poor prognosis of patients with colon cancer. And the potential signaling loop involving them may provide a helpful therapeutic target in prevention and treatment of colon cancer.

show abstract

Translation initiation in colorectal cancer

Cited by 12 publications

References 50 publications

Paip1, an Effective Stimulator of Translation Initiation, Is Targeted by WWP2 for Ubiquitination and Degradation

Paip1, an Effective Stimulator of Translation Initiation, Is Targeted by WWP2 for Ubiquitination and Degradation

Integrin β6 can be translationally regulated by eukaryotic initiation factor 4E: Contributing to colonic tumor malignancy

Protein expression of eIF4E and integrin αvβ6 in colon cancer can predict clinical significance, reveal their correlation and imply possible mechanism of interaction

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