BAP31, a newly defined cancer/testis antigen, regulates proliferation, migration, and invasion to promote cervical cancer progression

Abstract

Malignant tumors typically undergo an atavistic regression characterized by the overexpression of embryonic genes and proto-oncogenes, including a variety of cancer/testis antigens (CTAs) that are testis-derived and are not expressed or expressed in trace amounts in somatic tissues. Based on this theory, we established a new method to identify unknown CTAs, the spermatogenic cells-specific monoclonal antibody-defined cancer/testis antigen (SADA) method. Using the SADA method, we identified BAP31 as a novel CTA and confirmed that BAP31 expression is associated with progression and metastasis of several cancers, particularly in cervical cancer. We found that BAP31 was significantly upregulated in stage I, II, and III cervical cancer patients and highly correlated with poor clinic outcomes. We further demonstrated that BAP31 regulates cervical cancer cell proliferation by arresting the cell cycle at the G0/G1 stage and that depletion of BAP31 inhibits hyper-proliferation. Moreover, depletion of BAP31 inhibits cervical cancer cell invasion and migration by regulating the expression and subcellular localization of Drebrin, M-RIP, SPECC1L, and Nexilin, and then affect the cytoskeleton assemblage. Finally, the depletion of BAP31 prevents cervical cancer progression and metastasis in vivo. These findings provide a new method for identifying novel CTAs as well as mechanistic insights into how BAP31 regulates cervical cancer hyper-proliferation and metastasis.

A BAP31 intrabody induces gastric cancer cell death by inhibiting p27kip1 proteasome degradation

“…Increasing evidence shows that BAP31, which serves as a novel cancer antigen, is highly expressed in many types of carcinoma. Notably, BAP31 has been found to aid in the proliferation and metastasis of tumors, and its aberrant expression correlates with poor prognosis in patients . The Oncomine datasets showed that the expression level of BAP31 in human gastric intestinal‐type adenocarcinoma is significantly higher than that in the normal gastric mucosa, suggesting that BAP31 might be a tumor‐associated antigen of GC.…”

“…Notably, BAP31 has been found to aid in the proliferation and metastasis of tumors, and its aberrant expression correlates with poor prognosis in patients. [11][12][13]34 The Oncomine datasets showed that the expression level of BAP31 in human gastric intestinal-type adenocarcinoma is significantly higher than that in the normal gastric mucosa, suggesting that BAP31 might be a tumor-associated antigen of GC. By analyzing the relationship of BAP31 with different tumor-associated antigens, we found that BAP31 could apparently affect the expression level of p27 kip1 .…”

“…10 BAP31 was recently found to be highly expressed in many types of cancers, such as cervical cancer, colorectal cancer and liver cancer. [11][12][13] Furthermore, according to the statistical analysis of the Oncomine database (https://www.oncomine. org/), the expression of BAP31 in gastric intestinal-type adenocarcinoma is significantly higher than that in normal gastric mucosa ( Fig.…”

B-Cell Receptor-Associated Protein 31 Regulates the Expression of Valosin-Containing Protein Through Elf2

“…For instance, cycle-related proteins (cyclin D, cyclin E1, and cyclin E2) were significantly decreased in HeLa and SiHa cells transfected with siRNA-Bap31 compared with those in the control cells. The knockdown of Bap31 arrests the cell cycle at the G0/G1 phase Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry [34]. The protein levels of cyclin D1, cyclin E, CDK2, CDK4, Ki-67 and PCNA were decreased in shRNA-VCP-transfected cells [26].…”

Trial watch: Peptide-based vaccines in anticancer therapy

“…One specific class of TAAs is constituted by so-called “tumor neoantigens” (TNAs). 66-71 At odds with other variants of TAAs including oncofetal antigens and cancer-testis antigens, which can be expressed by healthy tissues (at least at some stage of development), 37,72-75 TNAs are produced as a consequence of genetic alterations that are highly specific for the tumor, or even portions thereof. 76-78 Similarly, TNAs that are fully tumor-specific occur upon the rearrangement of immunoglobulin-coding genes in clonal B-cell malignancies.…”