DNAJC24 is a potential therapeutic target in hepatocellular carcinoma through affecting ammonia metabolism

Abstract

Evolutionarily conserved heat shock proteins are involved in the heat shock response of cells in response to changes in the external environment. In normal tissues, heat shock proteins can help cells survive in a rapidly changing environment. Likewise, in malignant tumors heat shock proteins may help tumor cells cope with external stresses as well as the stress of treatment. In this way they become accomplices of malignant tumors. Here we demonstrated for the first time that high expression of DNAJC24 (a heat shock protein) shortens survival in patients with HCC by immunohistochemical staining of 167 paired hepatocellular carcinomas and paraneoplastic tissues as well as data from public databases. In vitro experiments demonstrated that stimuli such as hypoxia, starvation and heat could upregulate DNAJC24 expression in HCC cells through transcriptional regulation of HSF2, and high expression of DNAJC24 in HCC cells could promote the proliferation and motility of HCC cells. In addition, we also verified that targeting DNAJC24 under normal culture conditions can affect the proliferation and autophagy of HCC cells by interfering with ammonia metabolism, thereby inhibiting the malignant progression of HCC. Overall, we suggested that DNAJC24 may become a new target for the treatment of HCC.

TWF1 induces autophagy and accelerates malignant phenotype in lung adenocarcinoma via inhibiting the cAMP signaling pathway

“…33 Autophagy is generally considered to be a mechanism that allows cancer cells to maintain cellular homeostasis under either normal or stressful conditions. 34 Accumulating evidence has indicated that autophagy plays a complex role in cancer cell motility and invasion during tumor metastasis. 23 Depending on the tumor microenvironment, autophagy has been reported to play pro-and anti-metastasis roles.…”

“…In addition, PCSK9 was involved in the development of autophagy, as discovered in ischemic myocardial cells from a report in 2018 33 . Autophagy is generally considered to be a mechanism that allows cancer cells to maintain cellular homeostasis under either normal or stressful conditions 34 . Accumulating evidence has indicated that autophagy plays a complex role in cancer cell motility and invasion during tumor metastasis 23 .…”

Heat Shock Transcription Factor 2 Is Significantly Involved in Neurodegenerative Diseases, Inflammatory Bowel Disease, Cancer, Male Infertility, and Fetal Alcohol Spectrum Disorder: The Novel Mechanisms of Several Severe Diseases

“…Recently, Guo and his colleagues showed that high expression of DNAJC24 (HSP40 Member C24, a heat shock protein) occurs in hepatocellular carcinoma patients with shortened life span and that the transcription of DNAJC24 is regulated by HSF2 [ 94 ] ( Table 1 ).…”

“…Next, they performed the correlation analysis using the Cancer Genome Atlas (TCGA) database and determined that HSF2 expression is positively correlated with DNAJC24 higher than other HSFs. Additionally, HSF2 expression was higher in hepatocellular carcinoma tissues than in para-cancerous tissues, and the HSF2 expression level increased with tumor stage [ 94 ]. These data indicate that the HSF2-DNAJC24 pathway is also involved in the HSF2-mediated mechanism of hepatocellular carcinoma survival or progression.…”

DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT

“…10 Our previous study has demonstrated for the first time that DNAJC24 played an important role in tumor cell proliferation. 11 However, the role of DNAJC24 and the molecular mechanism in tumor progression deserve further investigation. Therefore, exploring the possibility of DNAJC24 as a novel biomarker and fully understanding the function of DNAJC24 in LUAD progression are crucial.…”