FASTKD2 promotes cancer cell progression through upregulating Myc expression in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers of the digestive system. Despite the development of novel therapeutic methods, including chemotherapy, radiotherapy, and molecular targeted therapy, the incidence rate of PDAC is almost equal to the mortality rate with 5-year overall survival rate less than 5%. Kras mutation is found in 95% of patient with PDAC specimens, but targeting Kras mutation do not benefit patients with pancreatic cancer in preclinical trials. c-Myc is one of the main effector molecules of the Kras signaling pathway. In this study, we found that dysregulation of FAST kinase-domain-containing protein 2 (FASTKD2) resulted in the poor prognosis of patients with PDAC. Then, we showed that FASTKD2 promoted pancreatic cancer cell proliferation and invasion. Importantly, we demonstrated that c-Myc was transcriptionally increased by FASTKD2/BRD4 axis and responsible for FASTKD2-mediated tumor growth and invasion in pancreatic cancer cells. Collectively, this study uncovered that FASTKD2 promoted cancer cell progression through upregulating Myc expression in pancreatic cancer. FASTKD2 might be a potential target for pancreatic cancer therapy.

Human Mitoribosome Biogenesis and Its Emerging Links to Disease

“…Other studies have suggested additional links between FASTKD2 and disease. A study found an association between dysregulated FASTKD2 and poor prognosis of patients with pancreatic ductal adenocarcinoma, through FASTKD2's role in promoting tumor growth and invasion, via upregulation of c-Myc expression [174]. Furthermore, RNA sequencing identified FASTKD2 as one of several mitochondria-related differentially expressed transcripts in astrocytes from patients with Alzheimer's disease, although no further characterization or validation were conducted [160].…”

USF1-CHCHD4 axis promotes lung adenocarcinoma progression partially via activating the MYC pathway

“…In addition, MYC oncoprotein expression is thought to be related to the output of major cellular processes including proliferation, apoptosis, differentiation, and metabolism [25]. An increasing number of studies have reported that some genes promote cancer progression by activating the MYC pathway [28][29][30]. For example, LCAT3 plays an oncogenic role in lung cancer by binding to FUBP1 to activate MYC [31].…”

FASTK family of genes linked to cancer

“…Knockdown of FASTKD4 lung cancer cells led to the inhibition of cell proliferation, migration, and invasion highlighting its role in tumour growth in lung cancer [ 23 ]. In the case of pancreatic adenocarcinoma, FASTK and FASTKD2 had also been involved in proliferation, invasion, and migration and hence poor prognosis [ 24 , 25 ]. Conversely, the overexpression of FASTKD3 in bladder cancer improved patient survival [ 26 ].…”