The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma

Casadonte²,

Molecular & Cellular Proteomics

et al. 2016

Lung cancer is the leading cause of cancer related death worldwide among both, men and woman with about 1.59 million reported deaths in 2012 (1). Two major lung cancer categories are discerned, namely small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) 1 , with the latter comprising ϳ85% of all cases. The two predominant histological NSCLC entities are adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) accounting for ϳ50 and 40% of all lung cancers, respectively (2).Because differentiation of NSCLC subtypes is crucial for the selection of chemotherapy regimens and subsequent molecular test strategies, precise subtyping is paramount. Therapeutic targets such as ALK translocations or activating mutations of the epidermal growth factor receptor (EGFR) have been found almost exclusively in ADC and these patients benefit from the respective molecularly tar-

Section: Discussionmentioning

confidence: 59%

Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens

Casadonte²,

Molecular & Cellular Proteomics

et al. 2016

“…At present, CLIC1 has been found to be closely related to many kinds of tumors. Several studies have shown that CLIC1 is expressed at a low level in normal gastric tissues and highly expressed in GC tissues [14-16]. It has also been found that the expression of CLIC1 in GC is closely related to the invasion and metastasis of lymph nodes and the infiltration of peripheral nerves, suggesting that CLIC1 is a potential tumor marker [7].…”

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

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.

Molecular Cancer Research

“…Despite its ubiquitous expression, CLIC1 has regularly been shown to be up-regulated in patients with malignant tumors of the brain, liver, lung, ovaries and gastro-intestinal tract and in many of these malignancies, CLIC1 expression correlates with aggressive disease and poor outcome (12, 19–22). In addition, CLIC1 has been shown to be over-expressed in the tumor vasculature indicating that CLIC1 plays an important role in the different aspects of tumor growth and metastasis (10).…”

Section: Discussionmentioning

confidence: 99%

“…CLIC1 is overexpressed in the tumor vasculature and frequently up-regulated in patients with cancers originating from the breast, lung and liver (10–12). Increasing concentrations of CLIC1 have also been detected in the serum of patients with aggressive ovarian cancer suggesting that CLIC1 could be useful as a tumor marker (13).…”

Section: Introductionmentioning

confidence: 99%

Relocation of CLIC1 Promotes Tumor Cell Invasion and Colonization of Fibrin

Gurski

Knowles

Basse

et al. 2015

Chloride intracellular channel 1 (CLIC1) has been shown to be up-regulated in various malignancies but its exact function remains unclear. Here, it is revealed that CLIC1 is critical for the stability of invadopodia in endothelial and tumor cells embedded in a 3-dimensional (3D) matrix of fibrin. Invadopodia stability was associated with the capacity of CLIC1 to induce stress fiber and fibronectin matrix formation following its β3 integrin (ITGB3)-mediated recruitment into invadopodia. This pathway, in turn, was relevant for fibrin colonization as well as slug (SNAI2) expression and correlated with a significant role of CLIC1 in metastasis in vivo. Mechanistically, a reduction of myosin light chain kinase (MYLK) in CLIC1- as well as β3 integrin-depleted cells suggests an important role of CLIC1 for integrin-mediated actomyosin dynamics in cells embedded in fibrin. Overall, these results indicate that CLIC1 is an important contributor to tumor invasion, metastasis and angiogenesis. Implications This study uncovers an important new function of CLIC1 in the regulation of cell-extracellular matrix interactions and ability of tumor cells to metastasize to distant organs.