The cancer testes antigen, HORMAD1, limits genomic instability in cancer cells by protecting stalled replication forks.

Tumors anomalously induce the expression of meiotic genes, which are otherwise restricted only to developing gametes. If and how these aberrantly expressed meiotic proteins influence DNA metabolism is not clear, but could have important implications for how tumors acquire and mitigate genomic instability. HORMAD1 is a highly conserved meiotic protein that is frequently expressed in lung adenocarincoma where its expression correlates with reduced patient survival and increased mutation burden.

The Cancer Testes Antigen, HORMAD1, is a Tumor-Specific Replication Fork Protection Factor.

Tumors frequently activate the expression of genes that are only otherwise required for meiosis. HORMAD1, which is essential for meiotic recombination in multiple species, is expressed in over 50% of human lung adenocarcinoma cells (LUAD). We previously found that HORMAD1 promotes DNA double strand break (DSB) repair in LUAD.

Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma.

Cancer testis antigens (CTAs) are proteins whose expression is normally restricted to the testis but anomalously activated in human cancer. In sperm, a number of CTAs support energy generation, however, whether they contribute to tumor metabolism is not understood. We describe human COX6B2, a component of cytochrome c oxidase (complex IV).

The testis protein ZNF165 is a SMAD3 cofactor that coordinates oncogenic TGFβ signaling in triple-negative breast cancer.

Cancer/testis (CT) antigens are proteins whose expression is normally restricted to germ cells yet aberrantly activated in tumors, where their functions remain relatively cryptic. Here we report that ZNF165, a CT antigen frequently expressed in triple-negative breast cancer (TNBC), associates with SMAD3 to modulate transcription of transforming growth factor β (TGFβ)-dependent genes and thereby promote growth and survival of human TNBC cells. In addition, we identify the KRAB zinc finger protein, ZNF446, and its associated tripartite motif protein, TRIM27, as obligate components of the ZNF165-SMAD3 complex that also support tumor cell viability.

EWSR1-FLI1 Activation of the Cancer/Testis Antigen FATE1 Promotes Ewing Sarcoma Survival.

Ewing sarcoma is characterized by a pathognomonic chromosomal translocation that generates the EWSR1-FLI1 chimeric transcription factor. The transcriptional targets of EWSR1-FLI1 that are essential for tumorigenicity are incompletely defined. Here, we found that EWSR1-FLI1 modulates the expression of cancer/testis (CT) antigen genes, whose expression is biased to the testes but is also activated in cancer.

Emerging Contributions of Cancer/Testis Antigens to Neoplastic Behaviors.

Tumors of nearly every origin activate the expression of genes normally restricted to gametogenic cells. These genes encode proteins termed cancer/testis (CT) antigens, since expression outside of their naturally immune-privileged site can evoke an immune response. Despite extensive efforts to exploit CT antigens as immunotherapeutic targets, investigation of whether these proteins participate in tumorigenic processes has lagged.

Genome Sequences of Five Bacteriophages Forming Cluster BG.

Cluster BG of the actinobacteriophage was formed upon discovery of five novel bacteriophages isolated by enrichment from their host, subsp. strain ATCC 10137. Four members of this cluster (BabyGotBac, Maih, TP1605, and YDN12) share over 89% average nucleotide identity, while the other (Xkcd426) has only 72% similarity to other cluster members.