Abstract
Cytoskeleton-associated protein 4 (CKAP4) is located in the rough endoplasmic reticulum (ER) and plays an important role in stabilizing the structure of ER. Meanwhile, CKAP4 is also found to act as an activated receptor at the cell surface. The multifunction of CKAP4 was gradually discovered with growing research evidence. In addition to the involvement in various physiological events including cell proliferation, cell migration, and stabilizing the structure of ER, CKAP4 has been implicated in tumorigenesis. However, the role of CKAP4 is still controversial in tumor biology, which may be related to different signal transduction pathways mediated by binding to different ligands in various microenvironments. Interestingly, CKAP4 has been recently recognized as a serological marker of several tumors and CKAP4 is expected to be a tumor therapeutic target. Therefore, deciphering the gene status, expression regulation, functions of CKAP4 in different diseases may shed new light on CKAP4-based cancer diagnosis and therapeutic strategy. This review discusses the publications that describe CKAP4 in various diseases, especially on tumor promotion and suppression, and provides a detailed discussion on the discrepancy.
Highlights
The results showed that the expression of Cytoskeleton-associated protein 4 (CKAP4) in hepatocellular carcinoma (HCC) tumor tissues was significantly higher than that in para-carcinoma normal tissues
We analyzed 173 intrahepatic cholangiocellular carcinoma (ICC) patient tissues; the results revealed that CKAP4 overexpression was observed in the great mass of ICC and associated with distant metastasis and lymph node metastasis (Li et al, 2013)
The results showed that the sensitivity of the serum CKAP4 is 70% and the specificity is 67.5%, and detection of serum CKAP4 increased the diagnostic efficacy especially in HCC patients with low or negative alpha-fetoprotein (AFP) (Li et al, 2016)
Summary
Recent studies have found that CKAP4 can be detected in the serum of HCC, pancreatic ductal adenocarcinoma, esophageal squamous cell carcinoma, and lung cancer patients (Li et al, 2016; Cheng et al, 2017; Yanagita et al, 2018; Kimura et al, 2019; Wang et al, 2019). These data demonstrate that CKAP4 as SP-A functional receptor is essential for SP-Amediated interactions with type II lung cells and the regulation of surfactant secretion and uptake (Table 1). Following CKAP4 knockdown, the inhibition effect of APF on T24 cell proliferation was eliminated, indicating the important role of the receptor in mediating the antiproliferation activity of APF in bladder cancer cells (Shahjee et al, 2010).
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