Overexpression of integrin αv correlates with poor prognosis in colorectal cancer

Ha, Sang Yun; Shin, Juyoun; Kim, Jeong Hoon; Kang, Myung Soo; Yoo, Hae-Yong; Kim, Hyeon-ho; Um, Sung-Hee; Kim, Seok-Hyung

doi:10.1136/jclinpath-2013-202163

Cited by 18 publications

(15 citation statements)

References 29 publications

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“…Subsequently, we examined the correlation of individual cell migration-associated genes such as integrins ( ITGA and ITGB ), cell adhesion molecules (E-selectin, VCAM1 and ICAM1 ), neuropilins ( NRP1 and NRP2 ) and epithelial-to-mesenchymal transition transcription factors ( ZEB1 and ZEB2 ), with AXL , MERTK and TYRO3 (Fig 2 and S3 Fig). Some of these genes, such as ITGA5 , E-selectin ( SELE ), VCAM1 , ICAM1 , NRP1 and NRP2 have previously been implicated in CRC progression [41–45]. These genes associated strongly with AXL .…”

Section: Resultsmentioning

confidence: 99%

The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer

et al. 2017

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The receptor tyrosine kinases (RTKs) TYRO3, AXL and MERTK (TAM) have well-described oncogenic functions in a number of cancers. Notwithstanding, TAM RTKs are also potent and indispensable inhibitors of inflammation. The combined deletion of Axl and Mertk in mice enhances chronic inflammation and autoimmunity, including increased inflammation in the gut and colitis-associated cancer. On the other hand, deletion of Tyro3 increases the risk of allergic responses. Therefore, the indiscriminate inhibition of these TAM RTKs could result in undesirable immunological diseases. Here we show that AXL, but not MERTK or TYRO3 expression is enhanced in late stage colorectal cancer (CRC) and AXL expression associates with a cell migration gene signature. Silencing AXL or the inhibition of AXL kinase activity significantly inhibits tumor cell migration and invasion. These results indicate that the selective inhibition of AXL alone might confer sufficient therapeutic benefit in CRC, while preserving at least some of the beneficial, anti-inflammatory effects of MERTK and TYRO3 RTKs.

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Section: Resultsmentioning

confidence: 99%

The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer

et al. 2017

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“…The tissues of non-small cell lung cancer were observed abnormal elevation of integrin αV expression that was believed to promote tumor proliferation and progression [23]. Overexpression of integrin αV correlates well with the shorter survival of patients with colorectal cancer [24]. Integrin αVβ3 mediates the interaction with extracellular matrix as an adhesion molecule, but overexpressed integrin αVβ3 initiates endothelial cell survival in anchorage independence and tumor metastasis without ECM ligand binding [5].…”

Section: Discussionmentioning

confidence: 99%

Sulfatide interacts with and activates integrin αVβ3 in human hepatocellular carcinoma cells

Wang

Dong

et al. 2016

Oncotarget

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Integrin αVβ3 is a malignant driver of anchorage-independence and tumor angiogenesis, but its dysregulation in hepatocellular carcinoma (HCC) remains unclear. In this study, we observed that sulfatide significantly promoted integrin αV(ITGAV) expression and wound closure in HCC. We also noted that elevated sulfatide profoundly stimulated integrin αVβ3 clustering and signaling. In the cells with integrin αVβ3 clustering induced by sulfatide, integrin β3 subunit was phosphorylated. Simultaneously, focal adhesion kinase (FAK), Src and paxillin were also phosphorylated. Treatment with FAK inhibitor resulted in robust suppression of FAK-Y397 and Src-Y416 phosphorylation stimulated by sulfatide, but not suppression of integrin β3 phosphorylation. Src inhibitors repressed Src-Y416 and FAK Y861 and Y925 phosphorylation, but not FAK-Y397 and integrin β3 phosphorylation. After mutation of integrin β3 (Y773F and Y785F), FAK or Src phosphorylation failed to be stimulated by sulfatide. Moreover, β3 Y773 and Y785 phosphorylation was suppressed by insulin-like growth factor receptor knockdown even in cells stimulated by sulfatide. In assays of immunoprecipitation and immunostaining with integrin αV or β3 antibody, labeled sulfatide was found in the complex and co-localized with integrin αVβ3. Taken together, this study demonstrated that elevated sulfatide bound to integrin αVβ3 and induced clustering and phosphorylation of αVβ3 instead of matrix ligand binding, triggering outside-in signaling.

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“…Additionally, Nakada et al [23] reported that ITGα3 is over-expressed in glioma stem-like cells and promotes invasion. Furthermore, evidence shows that overexpression of ITGαv is closely associated with the metastasis and progression of some cancers [24, 25]. …”

Section: Discussionmentioning

confidence: 99%

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

Mao

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. Methods: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. Results: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGβ1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGβ1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. Conclusions: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways.

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Overexpression of integrin αv correlates with poor prognosis in colorectal cancer

Abstract: Overexpression of integrin αv is associated with advanced T and N stage and as an independent prognostic factor in CRC.

Cited by 18 publications

References 29 publications

The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer

The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer

Sulfatide interacts with and activates integrin αVβ3 in human hepatocellular carcinoma cells

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

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