BackgroundKin17 is ubiquitously expressed at low levels in human tissue and participates in DNA replication, DNA repair and cell cycle control. Breast cancer cells are characterized by enabling replicative immortality and accumulated DNA damage. However, whether kin17 contributes to breast carcinogenesis remains unknown.Methodology/Principal FindingsIn this study, we show for the first time that kin17 is an important molecule related to breast cancer. Our results show that kin17 expression was markedly increased in clinical breast tumors and was associated with tumor grade, Ki-67 expression, p53 mutation status and progesterone receptor expression, which were assessed in a clinicopathologic characteristics review. Knockdown of kin17 inhibited DNA replication and repair, blocked cell cycle progression and inhibited anchorage-independent growth, while increasing sensitivity to chemotherapy in breast cancer cells. Moreover, kin17 silencing decreased EGF-stimulated cell growth. Furthermore, overexpression of kin17 promoted DNA replication and cell proliferation in MCF-10A.Conclusions/SignificanceOur findings indicate that up-regulation of kin17 is strongly associated with cellular proliferation, DNA replication, DNA damage response and breast cancer development. The increased level of kin17 was not only a consequence of immortalization but also associated with tumorigenesis. Therefore, kin17 could be a novel therapeutic target for inhibiting cell growth in breast cancer.

Induced pluripotent stem cells (iPSCs) and cancer cells share cellular similarities and transcriptomic profiles. Here, we show that an iPSCbased cancer vaccine, comprised of autologous iPSCs and CpG, stimulated cytotoxic antitumor CD8 + T cell effector and memory responses, induced cancer-specific humoral immune responses, reduced immunosuppressive CD4 + T regulatory cells, and prevented tumor formation in 75% of pancreatic ductal adenocarcinoma (PDAC) mice. We demonstrate that shared gene expression profiles of ''iPSC-cancer signature genes'' and others are overexpressed in mouse and human iPSC lines, PDAC cells, and multiple human solid tumor types compared with normal tissues. These results support further studies of iPSC vaccination in PDAC in preclinical and clinical models and in other cancer types that have low mutational burdens.

Over a century ago, it was reported that immunization with embryonic/fetal tissue could lead to the rejection of transplanted tumors in animals. Subsequent studies demonstrated that vaccination of embryonic materials in animals induced cellular and humoral immunity against transplantable tumors and carcinogen-induced tumors. Therefore, it has been hypothesized that the shared antigens between tumors and embryonic/fetal tissues (oncofetal antigens) are the key to anti-tumor immune responses in these studies. However, early oncofetal antigen-based cancer vaccines usually utilize xenogeneic or allogeneic embryonic stem cells or tissues, making it difficult to tease apart the anti-tumor immunity elicited by the oncofetal antigens vs. graft-vs.-host responses. Recently, one oncofetal antigen-based cancer vaccine using autologous induced pluripotent stem cells (iPSCs) demonstrated marked prophylactic and therapeutic potential, suggesting critical roles of oncofetal antigens in inducing anti-tumor immunity. In this review, we present an overview of recent studies in the field of oncofetal antigen-based cancer vaccines, including single peptide-based cancer vaccines, embryonic stem cell (ESC)- and iPSC-based whole-cell vaccines, and provide insights on future directions.