PLAC8 contributes to the malignant behaviors of cervical cancer cells by activating the SOX4-mediated AKT pathway

• Published in: Histochemistry and cell biology 2023-05, Vol.159 (5), p.439-451
• Main Authors: Deng, Boya, Zhang, Siyang, Zhou, Yingying, Zhu, Ying, Fei, Jing, Li, Ailin
• Format: Article
• Language: English
• Subjects: AKT protein; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cadherins - metabolism; Cell adhesion & migration; Cell Biology; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cervical cancer; Developmental Biology; Epithelial-Mesenchymal Transition; Female; Gelatinase A; Gelatinase B; Gene Expression Regulation, Neoplastic; Homeobox; Humans; Malignancy; Matrix metalloproteinase; Metalloproteinase; Morbidity; Original Paper; Proteins - metabolism; Proto-Oncogene Proteins c-akt - metabolism; siRNA; SOXC Transcription Factors - genetics; SOXC Transcription Factors - metabolism; Uterine Cervical Neoplasms; Vimentin; Zinc Finger E-box-Binding Homeobox 1 - genetics; Zinc Finger E-box-Binding Homeobox 1 - metabolism; Zinc finger proteins
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-022-02175-0

Cervical cancer (CC) is the primary cancer-related cause of morbidity and mortality in women. Previous studies have shown that placenta-specific 8 (PLAC8) has different functions in multiple malignancies. This study aimed to explore the function and regulatory mechanism of PLAC8 in CC. Bioinformatics and immunohistochemical analyses demonstrated that PLAC8 was significantly upregulated in CC tissues compared with normal tissues. Gain/loss-of-function experiments showed that siRNA-mediated knockdown of PLAC8 suppressed cell migration and invasion, while PLAC8 overexpression promoted cell motility. Moreover, PLAC8 was revealed to affect the epithelial–mesenchymal transition (EMT) process by upregulating epithelial (E)-cadherin and decreasing the expression of mesenchymal markers of EMT, including vimentin, zinc finger E-box binding homeobox 1 (ZEB1), neural (N)-cadherin, matrix metalloproteinase-9 (MMP-9), and MMP-2 in PLAC8-silenced cells. PLAC8 activated the AKT pathway, as proven by the downregulation of p-AKT Ser473 and p-AKT Thr308 expression after PLAC8 knockdown. Furthermore, PLAC8 overexpression upregulated the expression of sex-determining region Y-related high-mobility group box transcription factor 4 (SOX4), which is reported to mediate the activation of the AKT pathway, and SOX4 deficiency reversed the cellular functions caused by PLAC8 overexpression. Overall, the present study indicates that PLAC8 may facilitate CC development by activating the SOX4-mediated AKT pathway, suggesting that PLAC8 may serve as a potential biomarker for CC treatment. Graphical abstract