Down syndrome critical region 1 positively correlates with angiogenesis in hypopharyngeal cancer

Abstract

Hypopharyngeal carcinoma has one of the highest mortality rates of head and neck cancer, therefore, the identification of markers associated with the pathogenesis and development of hypopharyngeal cancer is critical. Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. Activation of the vascular endothelial growth factor (VEGF) signaling pathway upregulates DSCR1. The aims of the present study were to determine the expression levels of DSCR1 and VEGF‑C in hypopharyngeal cancer, and investigate the association between DSCR1 and angiogenesis in the disease. Tissue samples from 94 cases of pathologically confirmed hypopharyngeal squamous cell carcinoma were collected. The mRNA levels of DSCR1 and VEGF‑C in cancerous and paracancerous tissues were examined using semi‑quantitative reverse transcription‑polymerase chain reaction. Microvessel density (MVD) was counted, according to the number of cluster of differentiation 34‑positive cells. Spearman's correlation analysis was utilized to analyze the association between DSCR1 and angiogenesis. The relative mRNA expression levels of DSCR1 and VEGF‑C, and the MVD were significantly increased in the cancerous tissue samples from the patients with hypopharyngeal cancer, compared with the paracancerous tissue samples from these patients. Higher levels of DSCR1 and increased MVD were associated with poorly differentiated tumors and lymph node metastasis. The mRNA expression levels of DSCR1 were positively correlated with the mRNA levels of VEGF‑C in the cancerous tissues. The protein expression levels of DSCR1 were also positively correlated with MVD in the cancerous tissues. The results indicated that DSCR1 is involved in tumor angiogenesis in patients with hypopharyngeal cancer, and is closely associated with the progression of the disease.

Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling

“…DSCR1 could block calcineurin-NFAT signaling and keep a balance between pro- and anti-angiogenic factors through negative feedback in physiological conditions [9]. In the environment of tumor induced angiogenesis, the markedly raised level of VEGF leads to continuous activation of calcineurin-NFAT such that endogenous DSCR1 is not enough to neutralize the effect, resulting in the formation of a large number of new blood vessels that supply oxygen and nutrients to the tumor [10]. Studies have shown that upregulation of DSCR1 could reverse the over-activation of calcineurin-NFAT signaling and thus inhibit tumor growth and metastasis [11,12].…”

RCAN1 in the inverse association between Alzheimer’s disease and cancer

“…In addition, NFAT family members, downstream targets of RCAN1, are constitutively activated in several types of cancer, including breast cancer, pancreatic cancer, aggressive T cell lymphoma, Burkitt’s lymphoma, and diffuse large B cell lymphoma, suggesting that the inhibitory effect of RCAN1 on calcineurin/NFAT may be reduced by its downregulation [ 92 ]. However, increased expression of RCAN1.4 has also been detected in other types of cancer, such as hypopharyngeal cancer and Kaposi’s Sarcoma (KS) [ 93 - 94 ].…”

“…Several reports showed that increased expression of RCAN1.4 is associated with angiogenesis in hypopharyngeal cancer and Kaposi’s Sarcoma (KS) caused by Kaposi’s Sarcoma Herpesvirus (KSHV) [ 93 - 94 ], suggesting that increased RCAN1 expression may only be responsible for the inverse association of AD and some types but not all types of cancer. In addition, Ryeom et al reported that RCAN1 knock-out inhibits angiogenesis and tumor growth in mice [ 120 ].…”

Clinicopathological significance of RCAN2 production in gastric carcinoma

“…RCAN2 (also known as ZAKI‐4 , Dscr1/1 , MCIP2 , and Calcipressin2 ) was originally identified as a thyroid hormone (T3)‐responsive gene in cultured human skin fibroblasts, and was subsequently reported to function as a calcineurin regulator . Evidence of altered RCAN proteins in various human malignancies has been accumulating, and several studies have reported the inhibitory and facilitative effects of RCAN proteins on cancer cell growth . Our previous study clarified that KRAS mutations in colorectal cancer (CRC) lead to decreased RCAN2 expression, resulting in tumour proliferation because of derepression of the calcineurin–NFATc signalling pathway .…”

“…11,12 Evidence of altered RCAN proteins in various human malignancies has been accumulating, and several studies have reported the inhibitory and facilitative effects of RCAN proteins on cancer cell growth. [13][14][15][16] Our previous study clarified that KRAS mutations in colorectal cancer (CRC) lead to decreased RCAN2 expression, resulting in tumour proliferation because of derepression of the calcineurin-NFATc signalling pathway. 17 To date, RCAN proteins, including RCAN2, have not been investigated in GC.…”