Signaling and regulatory mechanisms of integrin ανβ6 on the apoptosis of colon cancer cells

Zhang, Zhaoyang; Xu, Kesen; He, Qin; Niu, Weibo; Wang, Jiayong; Yue-tang, Mi; Wang, Jinshen; Wang, Guoqiang; Yang, Guangli; Ni, Jun

doi:10.1016/j.canlet.2008.02.054

Cited by 39 publications

(31 citation statements)

References 26 publications

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“…The interaction of integrins with extracellular ligands is regulated from inside the cell through the short cytoplasmic α-and β-integrin tails, and transmits biochemical and mechanical signals to the cytoskeleton to change cell shape, behavior and fate (19). ITGAVB6 has a role in the inhibition of colon cancer cell apoptosis through targeting the mitochondrial pathway (20). Another study (21) demonstrated that antisense ITGAV and ITGB3 inhibited tumor vascularization and growth, but enhanced the apoptosis of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Detection of differentially expressed genes and association with clinicopathological features in laryngeal squamous cell carcinoma

Shen

Qian

et al. 2012

Oncology Letters

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Abstract. Head and neck cancer is a significant health problem worldwide. Early detection and prediction of prognosis will improve patient survival and quality of life. The aim of this study was to identify genes differentially expressed between laryngeal cancer and the corresponding normal tissues as potential biomarkers. A total of 36 patients with laryngeal squamous cell carcinoma were recruited. Four of these cases were randomly selected for cDNA microarray analysis of the entire genome. Using semi-quantitative RT-PCR and western blot analysis, the differential expression of genes and their protein products, respectively, between laryngeal cancer tissues and corresponding adjacent normal tissues was verified in the remaining 32 cases. The expression levels of these genes and proteins were investigated for associations with clinicopathological parameters taken from patient data. The cDNA microarray analysis identified 349 differentially expressed genes between tumor and normal tissues, 112 of which were upregulated and 237 were downregulated in tumors. Seven genes and their protein products were then selected for validation using RT-PCR and western blot analysis, respectively. The data demonstrated that the expression of SENP1, CD109, CKS2, LAMA3, ITGAV and ITGB8 was increased, while LAMA2 was downregulated in laryngeal cancer compared with the corresponding normal tissues. Associations between the expression of these genes and clinicopathological data from the patients were also established, including age, tumor classification, stage, differentiation and lymph node metastasis. Our current study provides the first evidence that these seven genes may be differentially expressed in laryngeal squamous cell carcinoma and also associated with clinicopathological data.Future study is required to further confirm whether detection of their expression can be used as biomarkers for prediction of patient survival or potential treatment targets. IntroductionHead and neck cancer is the sixth most common type of cancer in the world, accounting for more than 540,000 new cases and 271,000 mortalities each year (1). These cancers occur in the lips, oral cavity, nasal cavity, paranasal sinuses, pharynx and larynx, 90% of which are squamous cell carcinomas. They significantly affect long-term survival and the quality of life of patients. The development of novel strategies is required for prevention and early detection, to reduce cancer incidence and overcome problems associated with treatment of late-stage tumors. Improved prediction of outcome will lead to treatment decisions that prolong patients' survival and quality of life.Predictions concerning the outcome of head and neck cancers are currently based mostly on clinicopathological features, including tumor stage, differentiation, size and regional lymph node or distant metastasis. However, increasing numbers of studies utilize aberrant gene expression and genomic and epigenetic alterations to predict prognosis.It has been established that tobacco smoke and alcohol consump...

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Section: Discussionmentioning

confidence: 99%

Detection of differentially expressed genes and association with clinicopathological features in laryngeal squamous cell carcinoma

Shen

Qian

et al. 2012

Oncology Letters

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“…αvβ6 also is involved with the inhibition of apoptosis in colon cancer cells through the mitochondrial pathway. When this integrin is blocked, activity of caspase-3, caspase-9, and Bax increase, while Bcl-2 and activity of extracellular signalregulated kinase decreases in colon cancer cells [52], suggesting that this integrin plays an important role in apoptosis.…”

Section: Integrin αVβ6 and αVβ5mentioning

confidence: 98%

Important role of integrins in the cancer biology

Rathinam

Alahari

2010

Cancer Metastasis Rev

201

167

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Adhesion of breast cancer cells is supported by various integrins. Cell adhesion is critical for maintenance of both three-dimensional and normal function of these tissues. Several integrins have been shown to have higher expression levels in metastatic cancers and have been implicated in degrading basement membrane by interacting with proteolytic enzymes. This suggests that a group of integrins plays an important role in migration and invasion through the remodeling of the extracellular matrix. In this review, we highlight recent advances in our understanding of how integrins regulate breast cancer through modulation of the actin cytoskeleton and the mechanisms that regulate this process. Also, we highlight the importance of integrin-binding proteins in cell migration and mechanisms that operate in invasive cells, during breast cancer progression.

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“…Its expression has been known happening in different epithelial cancers (lung, oropharynx, colon, breast, ovary, and pancreas), as well as in tissue remodeling events (e.g., wound healing, fibrosis) [4,5]. These years, we have demonstrated that integrin αvβ6 can play a vital role in tumor metastasis, invasion, anti-apoptosis, and chemoresistance in colon cancer [6][7][8][9][10][11], and it has been recognized as an independent unfavorable prognostic indicator in human aggressive gastric and colonic carcinomas [5,12,13].…”

Section: Introductionmentioning

confidence: 95%

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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Signaling and regulatory mechanisms of integrin ανβ6 on the apoptosis of colon cancer cells

Cited by 39 publications

References 26 publications

Detection of differentially expressed genes and association with clinicopathological features in laryngeal squamous cell carcinoma

Detection of differentially expressed genes and association with clinicopathological features in laryngeal squamous cell carcinoma

Important role of integrins in the cancer biology

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

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