PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK.

Abstract

Background: The progressive, multifactorial and multistep dynamic process of metastasis is the primary cause of breast cancer (BC) lethality. PROX1 (Prospero-related homeobox 1), as a type of transcription factor that plays a key role in the formation of lymphatic vessels in animal embryonic development, has been proven to promote or suppress cancer in a variety of malignant tumors. However, molecular mechanisms behind PROX1 induced breast cancer metastases remain elusive. Methods: Changes of PROX1 expression and clinical significance of PROX1 in BC were evaluated by BC tissue, as well as public database. The functional role of PROX1 in metastases BC was analyzed by transwell assay in vitro, and by lung metastases model of nude mice in vivo via lentivirus mediated knockdown assays. Mechanism studies were performed by public database screening, western blot and PCR assay, immunoprecipitation, immunofluorescence staining and luciferase promoter assays. Results: In this study, we found that PROX1 was upregulated in breast cancer tissues; increased PROX1 expression in breast cancer was associated with tumor size, lymph node metastasis, ER and PR status. Meanwhile, PROX1 can promote breast cancer invasion and metastasis in vitro and in vivo. Furthermore, PROX1 can interact with hnRNPK to activate WNT/β-catenin signaling in breast cancer cells. Moreover, the interaction of PROX1 and hnRNPK inhibits the ubiquitination of hnRNPK, and subsequently activates WNT pathway to promote the invasion and metastasis of breast cancer. Conclusions: In conclusion, our findings indicated PROX1 contributes to breast cancer EMT and metastasis and serves as a candidate diagnostic biomarker and promising therapeutic target for breast cancer.

• Authors: Lizhe Zhu, Qi Tian, Huan Gao, Kaijie Wu, Bo Wang, Guanqun Ge, Siyuan Jiang, Ke Wang, Can Zhou, Jianjun He, Peijun Liu, Yu Ren, Bin Wang
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 18 Issue 5 Pg. 2032-2046 ( 2022) ISSN: 1449-2288 [Electronic] Australia
• PMID: 35342346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Heterogeneous-Nuclear Ribonucleoprotein K
• Homeodomain Proteins
• Transcription Factors
• Tumor Suppressor Proteins
• beta Catenin
• prospero-related homeobox 1 protein
• HNRNPK protein, human

Topics

• Animals
• Breast Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Heterogeneous-Nuclear Ribonucleoprotein K (metabolism)
• Homeodomain Proteins
• Humans
• Mice
• Mice, Nude
• Neoplasm Metastasis
• Transcription Factors (metabolism)
• Tumor Suppressor Proteins
• Wnt Signaling Pathway (genetics)
• beta Catenin (genetics, metabolism)