Home Neoplasma 2023 Neoplasma Vol.70, No.6, p. 761–776, 2023

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Neoplasma Vol.70, No.6, p. 761–776, 2023

Title: CCDC86 promotes the aggressive behavior of nasopharyngeal carcinoma by positively regulating EGFR and activating the PI3K/Akt signaling
Author: Zhi Wang, Tao Zhou, Xubo Chen, Xinhua Zhu, Bing Liao, Jianguo Liu, Siqi Li, Ting Tan, Yuehui Liu

Abstract: Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. A number of studies have confirmed that coiled-coil domain-containing protein 86 (CCDC86) plays an important role in the pathogenesis of lymphoma but the role of CCDC86 in NPC has not yet been reported. Here, in vivo and in vitro experiments were conducted to explore whether CCDC86 plays a role in the pathogenesis of NPC and to identify the specific mechanism. We found that CCDC86 was highly expressed in NPC tissues and cells, and the expression level of CCDC86 was correlated with the prognosis of patients with advanced NPC. CCDC86 promoted the proliferation, invasion, and migration of NPC cells in vivo and in vitro by promoting the EMT process and upregulating the expression of MMPs. Then, we confirmed that EGFR is a downstream target gene of CCDC86 and that CCDC86 can promote the proliferation, invasion, and migration of NPC cells by upregulating the expression of EGFR and activating downstream PI3K/Akt. Furthermore, we confirmed that CCDC86 did not directly bind to EGFR but positively regulated EGFR by binding to NPM1. CCDC86 is expected to be used as a novel biomarker and therapeutic target for predicting the prognosis of NPC.
Key words: nasopharyngeal carcinoma; CCDC86; invasion and migration; EGFR; PI3K-Akt signaling

Neoplasma Vol.70, No.6, p. 777–786
CHAC1 promotes cell ferroptosis and enhances radiation sensitivity in thyroid carcinoma
Xinlin Yang, Miao Zhang, Wei Xia, Zhongchao Mai, Ying Ye, Bin Zhao, Yanan Song
1Department of Nuclear Medicine, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Central Laboratory, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3General Surgery Department, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
*Correspondence: zhaobin0727@sina.com; ynsongh7@126.com
#Contributed equally to this work.

Received January 3, 2023 / Accepted November 29, 2023
ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) is involved in intracellular glutathione depletion, ferroptosis, and tumorigenesis. The functional role of CHAC1 expression in thyroid carcinoma has not yet been established. The present study aimed to investigate the impact and mechanisms of CHAC1 on ferroptosis and radiation sensitivity in thyroid carcinoma. CHAC1 expression was examined in tumor tissue specimens and microarrays and thyroid carcinoma cell lines. CHAC1 was silenced or overexpressed by lentivirus transfection in thyroid carcinoma cells. Cell viability and lipid ROS levels were evaluated by Cell Counting Kit-8 and flow cytometry, respectively. The effect of CHAC1 on tumor growth in vivo was also measured. Ferroptosis-related proteins were measured by western blotting. CHAC1 expression was decreased in patients with thyroid carcinoma, and overexpression of CHAC1 suppressed cell viability of BCPAP cells and tumor growth in xenografted nude mice. Exposure to Ferrostatin-1, a ferroptosis inhibitor, significantly attenuated the inhibitory effects of CHAC1 overexpression on cell viability. In CHAC1-overexpressing BCPAP cells, ferroptosis was induced as indicated by increased lipid ROS production and PTGS2 expression. Knocking down of CHAC1 in K1 cells significantly induced cell viability, reduced lipid ROS production and PTGS2 expression, and enhanced GPX4 expression. Such effects were attenuated by RSL3, a ferroptosis inducer. Furthermore, we showed that CHAC1 overexpression enhanced radiation sensitivity in BCPAP cells as indicated by decreased cell viability, while CHAC1 knockdown had reversed effects in K1 cells as indicated by increased cell viability. Taken together, CHAC1 overexpression promoted ferroptosis and enhanced radiation sensitivity in thyroid carcinoma.
Key words: thyroid carcinoma; CHAC1; ferroptosis; GPX4

Neoplasma Vol.70, No.6, p. 787–795
Innervation density and types of nerves in prostate cancer
Filip Blasko, Lucia Krivosikova, Pavel Babal, Jan Breza, Branislav Trebaticky, Roman Kuruc, Boris Mravec, Pavol Janega1Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia; 2Biomedical Research Center, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia; 3Institute of Pathological Anatomy, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia; 4Department of Pediatric Urology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia; 5Department of Urology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia; 6Health Care Surveillance Authority of the Slovak Republic, Bratislava, Slovakia
*Correspondence: lucia.krivosikova@fmed.uniba.sk; pavel.babal@fmed.uniba.sk

Received November 16, 2023 / Accepted December 20, 2023
Innervation of cancerous tissue represents an important pathway enabling the nervous system to influence the processes associated with the initiation, progression, and metastasis of a neoplastic process. In the context of prostate cancer, several papers report the presence of innervation and its modulating effect on the cancer prognosis. However, most of the data are experimental, with limited information on human prostate cancer innervation. Morphometric analysis of archival prostate specimen immunohistochemistry with neural markers PGP9.5 and S100 showed a significant decrease of nerve density in the prostate cancer (n=44) compared to the normal prostate tissue (n=18) and benign prostatic hyperplasia (n=28). Sympathetic nerves were detected with TH, parasympathetic with VAChT, and sensory nerves with SP and CGRP protein detection. Dual immunofluorescence revealed numerous sympathetic nerves in normal prostate and benign prostatic hyperplasia, especially in the peripheral parts. Only a few parasympathetic nerves were found between the glands and in the peripheral parts of the prostate and benign hyperplasia. Sporadic positivity for sensory innervation was present only in approximately 1/10 of nerve fibers, especially in the larger nerves. The pattern of innervation in prostate cancer was analogous to that in normal prostate gland and benign prostatic hyperplasia but there was a significantly lower amount of all nerve types, especially in high-grade carcinoma cases. Although not significant, there was a tendency of decreasing innervation density with increasing Gleason score. Regarding the low density of nerves in prostate carcinoma, the significantly lower PCNA counts in nerves of the cancer specimens cannot be ascribed to lower proliferation activity. Our data confirmed the lower nerve density in the prostate cancer compared to the benign prostate tissue. We could not approve an increased nerve proliferation activity in prostate cancer. All nerve types, most the sympathetic, less the parasympathetic, and the sensory nerves, are present in prostate cancer. The highest nerve density at the periphery of the cancer tissue implies this to be the result of an expansive tumor growth. It is evident that the results of experimental prostate cancer models can be applied to human pathology only to a certain extent. The relation between the range of innervation and the biology of prostate cancer is very complex and will require more detailed information to be applied in therapeutic solutions.

Keywords: neurobiology of cancer; cancer innervation; sympathetic nerves; parasympathetic nerves; sensory nerves; prostate cancer; benign prostatic hyperplasia
Published online: 19-Jan-2024
Year: 2023, Volume: 70, Issue: 6 Page From: 761, Page To: 776

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