Intracellular Chloride Ion Channel Protein-1 Expression in Clear Cell Renal Cell Carcinoma

Abstract

Background/Aim: Chloride intracellular channel 1 (CLIC1) represents a promising target for personalized therapy. Our aim was to assess CLIC1 expression in clear cell renal cell carcinoma (cc RCC) and identify its possible prognostic role. Materials and Methods: Fifty cases of cc RCC were evaluated and selected for immunohistochemistry. CLIC1 expression was correlated with tumor grade, invasion and heterogeneity. Results: A total of 87.5% of the cases were CLIC1 positive, with either a homogeneous (31.42%) or a heterogeneous (68.57%) pattern. Low, mild and strong CLIC1 expressing tumors were defined based on nuclear (N), cytoplasmic (C), membrane (M) or combinations of them (NC, NM, CM, NCM) in terms of CLIC1 distribution. A significant correlation was found between tumor grade and percent of positive tumor cells (p=0.017). For G3 tumors, CLIC1 cytoplasmic expression was strongly correlated with high expression status (p=0.025) and tumor heterogeneity (p=0.004). CLIC1 expression was also correlated with metastasis (p=0.046).

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

“…Previous research has shown that altered expression of particular genes may affect ESCC cell metastasis, invasion, apoptosis and proliferation [15][16][17] . Our results agree with the fact that carcinoma cell metastasis and invasion are closely associated with abnormal cell adhesion, endodermal cell division and nuclear division [18][19][20] . Extracellular matrix (ECM), is a critical component of the cancer cell niche, it can provide the tissue with the mechanical support and also mediate the cell-microenvironment interactions 21,22 .…”

Modeling Neoplastic Growth in Renal Cell Carcinoma and Polycystic Kidney Disease

“…The cytoplasmic chloride ion channel protein-1 (CLIC1) is normally expressed in the glomerulus and epithelial cells of the kidney proximal tubules [129]. CLIC1 is overexpressed in many tumor types [130] and drives glioblastoma cell growth and proliferation [131]. In response to oxidative stimuli and malignant transformation, CLIC1 translocates from the cytoplasm to the cell membrane [132][133][134], where it functions as a selective chloride channel that affects cell cycle regulation, cell size, membrane potential, and cell proliferation/differentiation [130,135].…”

“…CLIC1 is overexpressed in many tumor types [130] and drives glioblastoma cell growth and proliferation [131]. In response to oxidative stimuli and malignant transformation, CLIC1 translocates from the cytoplasm to the cell membrane [132][133][134], where it functions as a selective chloride channel that affects cell cycle regulation, cell size, membrane potential, and cell proliferation/differentiation [130,135]. As expected, high CLIC1 expression has been found in 50 resected samples of human ccRCC in both malignant tissue and sites of intravascular invasion, with G3 tumors displaying the most heterogeneous CLIC1 distribution [130].…”

Exosomal CLIC1 released by CLL promotes HUVECs angiogenesis by regulating ITGβ1‐MAPK/ERK axis

“…The chloride intracellular channel 1 (CLIC1) belongs to p64 family, which mainly exists in the nucleus, but also in the cytoplasm and cell membrane 11,12 . CLIC1, expressed in multiple tissues and organs, is highly conserved throughout evolution and its expression level varies little among different species.…”