TY  - EJOU
AU  - Tang, Yi 
AU  - Situ, Minyi 
AU  - Wu, Zhiming 
AU  - Wang, Yanjun 
AU  - Deng, Xinpei 
AU  - Liu, Zhicheng 
AU  - Guo, Shengjie 
AU  - Zhou, Qianghua 
AU  - Yuan, Gangjun 
AU  - Tan, Xingliang 
AU  - Yao, Kai 

TI  - TROP-2 Promotes Cell Proliferation via the AKT-Mediated PKC<b>α</b> Pathway and Is a Novel Target for Antibody-Drug Conjugates in Penile Carcinoma
T2  - Oncology Research

PY  - 2025
VL  - 33
IS  - 12
SN  - 1555-3906

AB  -  <b>Background:</b> Current chemotherapy treatments, including the TIP (Taxol, Ifosfamide, Cisplatin) regimen, have shown limited effects but strong side effects in advanced Penile squamous cell carcinoma (PSCC) patients. Trophoblast cell-surface antigen-2 (TROP-2) is a novel target for antibody-drug conjugate (ADC) drugs and has been proven to be effective in several human cancers. This study aimed to explore the biological function and potential of the ADC target in PSCC cells. <b>Methods:</b> A total of 196 PSCC tumor tissue specimens and clinicopathological data were collected. TROP-2 expression was detected by IHC, and the correlation between TROP-2 expression and the clinicopathological data of patients was analysed through statistical methods. Then, a series of <i>in vivo</i> and <i>in vitro</i> experiments were conducted to investigate the mechanism by which TROP-2 promotes PSCC cell proliferation. Additionally, the efficacy of TROP-2-targeted ADC and cisplatin was tested in PSCC cell lines and animal models. <b>Results:</b> Immunohistochemistry (IHC) revealed that TROP-2 was highly expressed in 60.2% of tumor specimens, and statistical analysis revealed that high TROP-2 expression correlated with advanced pT and pN stages and extranodal extension (ENE), as well as poor prognosis. Knockdown of TROP-2 inhibited the proliferation of PSCC cells both <i>in vivo</i> and <i>in vitro</i>, and this inhibitory effect was later proven to be mediated by protein kinase B (AKT), which is involved in the protein kinase C alpha (PKCα) signalling pathway. Furthermore, compared with cisplatin, TROP-2 targeted ADC could achieve an equivalent inhibitory effect on the proliferation of PSCC both <i>in vivo</i> and <i>in vitro</i>. <b>Conclusion:</b> TROP-2 promoted PSCC cell proliferation via AKT/PKCα-dependent pathway, and TROP-2-targeted ADC-drug has a gratifying inhibitory effect on PSCC proliferation both <i>in vivo</i> and <i>in vitro</i>.
KW  - Penile squamous cell carcinoma; trophoblast cell-surface antigen-2; protein kinase B; cell proliferation; targeted therapy

DO  - 10.32604/or.2025.066184