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Aberrant activation of embryogenesis-related molecular programs in urothelial bladder cancer (BC) is associated with stemness features related to oncogenic dedifferentiation and tumor metastasis. Recently, we reported that overexpression of transcription factor CP2-like protein-1 (TFCP2L1) and its phosphorylation at Thr177 by cyclin-dependent kinase-1 (CDK1) play key roles in regulating bladder carcinogenesis. However, the clinical relevance and therapeutic potential of this novel CDK1-TFCP2L1 molecular network remain elusive. Here, we demonstrated that inhibitor of DNA binding-2 (ID2) functions as a crucial mediator by acting as a direct repressive target of TFCP2L1 to modulate the stemness features and survival of BC cells. Low ID2 and high CDK1 expression were significantly associated with unfavorable clinical characteristics. TFCP2L1 downregulated ID2 by directly binding to its promoter region. Consistent with these findings, ectopic expression of ID2 or treatment with apigenin, a chemical activator of ID2, triggered apoptosis and impaired the proliferation, suppressed the stemness features, and reduced the invasive capacity of BC cells. Combination treatment with the specific CDK1 inhibitor RO-3306 and apigenin significantly suppressed tumor growth in an orthotopic BC xenograft animal model. This study demonstrates the biological role and clinical utility of ID2 as a direct target of the CDK1-TFCP2L1 pathway for modulating the stemness features of BC cells.

Translating the titles of narrative texts is a sui generis operation in the sense that the ontological conditions and the pragmatic functions of the title considerably predetermine the translator’s task. This article intends to give an account of the three functions of a title – designative, metalinguistic and seductive (the title as rigid designator or dense texture of meaning; synecdoche or interpretative key; whetting the appetite or advertising) – that shed light on the pragmatic issues encountered in translating titles. If the designative function of a title is oriented to the work as a referential object, the metalinguistic function is oriented to the text as an interpretive object. As for the seductive function, it turns to the outside, or in other words, to the public. In the case of translation or retranslation of a title, three functions come into play at the same time, but one of the functions can get the upper hand on the other two.