KIN17 Promotes Tumor Metastasis by Activating EMT Signaling in Luminal-A Breast Cancer

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2021 May 19

PMID 34008927

Citations 7

Authors

Qiyuan Huang

Kashif Rafiq Zahid

Jinsi Chen

Xiangxiong Pang

Meifeng Zhong

Hongling Huang

Weifeng Pan

Jingxin Yin

Umar Raza

Jiamin Zeng

Xinhong Zhu

Tao Zeng

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer (BC), the most common cause of cancer death in women, overtook lung cancer as the leading cause of cancer worldwide in 2020. Although many studies have proposed KIN17 as a biomarker of tumorigenesis in different cancer types, its role in tumor metastasis, particularly in BC metastasis, has been underexplored. This study aimed to explore the role of KIN17 in BC metastasis.

Methods: Survival analyses was performed to identify the association between KIN17 expression and BC patient survival in silico. Using lentivirus constructs, we developed bidirectional KIN17 expression (KD, knockdown; OE, overexpression) cellular models of luminal-A (Lum-A) breast cancer MCF-7 cells. We performed in vitro wound healing, transwell with and without Matrigel assays, and in vivo tail-vein metastasis assay to evaluate the migration and invasion abilities of MCF-7 with stable KIN17 knockdown or overexpression. Western blotting was performed to compare the changes in protein expression.

Results: We found that KIN17 expression was associated with poor overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS) and post-progression survival (PPS), particularly in Lum-A breast cancer patients. Later, we found that KIN17 knockdown inhibited migration and invasion of MCF-7 cells via regulating EMT-associated signaling pathways in vitro and decreases metastatic spread of the disease in vivo. In contrast, KIN17 overexpression promoted migration and invasion of MCF-7 cells in vitro and increased the metastatic spread of the disease in vivo.

Conclusions: Overall, our findings provide preliminary data which suggests KIN17 of importance to target in metastatic Lum-A patients.

Citing Articles

Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.

Petrella S, Colombo M, Marabese M, Grasselli C, Panfili A, Chiappa M Int J Mol Sci. 2025; 26(2).

PMID: 39859203 PMC: 11765470. DOI: 10.3390/ijms26020472.

Regulation of pancreatic cancer cells by suppressing KIN17 through the PI3K/AKT/mTOR signaling pathway.

Li Q, Yang Y, Lin X, Chu L, Chen H, Chen L Oncol Rep. 2025; 53(2.

PMID: 39791213 PMC: 11736091. DOI: 10.3892/or.2025.8864.

Exosomal miR-552-5p Regulates the Role of NK Cells in EMT of Gastric Cancer via the PD-1/PD-L1 Axis.

Qin J, Yang J, Cui H, Feng C, Liu A J Cancer. 2025; 16(2):406-416.

PMID: 39744482 PMC: 11685699. DOI: 10.7150/jca.102360.

KIN17 functions in DNA damage repair and chemosensitivity by modulating RAD51 in hepatocellular carcinoma.

Huang X, Dai Z, Zeng B, Xiao X, Zahid K, Lin X Hum Cell. 2024; 37(5):1489-1504.

PMID: 38935235 DOI: 10.1007/s13577-024-01096-5.

Kin17 regulates proper cortical localization of Miranda in Drosophila neuroblasts by regulating Flfl expression.

Connell M, Xie Y, Deng X, Chen R, Zhu S Cell Rep. 2024; 43(3):113823.

PMID: 38386552 PMC: 10980573. DOI: 10.1016/j.celrep.2024.113823.

References

Wang M, Ren D, Guo W, Huang S, Wang Z, Li Q . N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells. Int J Oncol. 2015; 48(2):595-606. DOI: 10.3892/ijo.2015.3270. View

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

Tsang J, Tse G . Molecular Classification of Breast Cancer. Adv Anat Pathol. 2019; 27(1):27-35. DOI: 10.1097/PAP.0000000000000232. View

Mazin A, Milot E, Devoret R, Chartrand P . KIN17, a mouse nuclear protein, binds to bent DNA fragments that are found at illegitimate recombination junctions in mammalian cells. Mol Gen Genet. 1994; 244(4):435-8. DOI: 10.1007/BF00286696. View

Labernadie A, Kato T, Brugues A, Serra-Picamal X, Derzsi S, Arwert E . A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat Cell Biol. 2017; 19(3):224-237. PMC: 5831988. DOI: 10.1038/ncb3478. View

Zheng X, Carstens J, Kim J, Scheible M, Kaye J, Sugimoto H . Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015; 527(7579):525-530. PMC: 4849281. DOI: 10.1038/nature16064. View

Alizadeh A, Shiri S, Farsinejad S . Metastasis review: from bench to bedside. Tumour Biol. 2014; 35(9):8483-523. DOI: 10.1007/s13277-014-2421-z. View

Xiong W, Cao X, Zeng Y, Qin X, Zhu M, Ren J . Astrocytic Epoxyeicosatrienoic Acid Signaling in the Medial Prefrontal Cortex Modulates Depressive-like Behaviors. J Neurosci. 2019; 39(23):4606-4623. PMC: 6554635. DOI: 10.1523/JNEUROSCI.3069-18.2019. View

Le M, Haddad D, Ling A, Li C, So C, Chopra A . Kin17 facilitates multiple double-strand break repair pathways that govern B cell class switching. Sci Rep. 2016; 6:37215. PMC: 5112545. DOI: 10.1038/srep37215. View

10.

Ramos A, Gaspar V, Kelmer S, Sellani T, Batista A, De Lima Neto Q . The kin17 Protein in Murine Melanoma Cells. Int J Mol Sci. 2015; 16(11):27912-20. PMC: 4661930. DOI: 10.3390/ijms161126072. View

11.

Huber M, Kraut N, Beug H . Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005; 17(5):548-58. DOI: 10.1016/j.ceb.2005.08.001. View

12.

Angulo J, Moreau P, Maunoury R, Laporte J, Hill A, Bertolotti R . KIN, a mammalian nuclear protein immunologically related to E. coli RecA protein. Mutat Res. 1989; 217(2):123-34. DOI: 10.1016/0921-8777(89)90064-5. View

13.

Mazin A, Timchenko T, Schreiber V, Angulo J, de Murcia G, Devoret R . Kin17, a mouse nuclear zinc finger protein that binds preferentially to curved DNA. Nucleic Acids Res. 1994; 22(20):4335-41. PMC: 331959. DOI: 10.1093/nar/22.20.4335. View

14.

Jiang Q, Xiong C, Lv Y . Kin17 facilitates thyroid cancer cell proliferation, migration, and invasion by activating p38 MAPK signaling pathway. Mol Cell Biochem. 2020; 476(2):727-739. DOI: 10.1007/s11010-020-03939-9. View

15.

Santamaria E, Munoz J, Fernandez-Irigoyen J, Prieto J, Corrales F . Toward the discovery of new biomarkers of hepatocellular carcinoma by proteomics. Liver Int. 2007; 27(2):163-73. DOI: 10.1111/j.1478-3231.2007.01447.x. View

16.

Biard D, Kannouche P, Mauffrey P, Apiou F, Angulo J . Ectopic expression of (Mm)Kin17 protein inhibits cell proliferation of human tumor-derived cells. Exp Cell Res. 1999; 250(2):499-509. DOI: 10.1006/excr.1999.4515. View

17.

Zeng T, Gao H, Yu P, He H, Ouyang X, Deng L . Up-regulation of kin17 is essential for proliferation of breast cancer. PLoS One. 2011; 6(9):e25343. PMC: 3183049. DOI: 10.1371/journal.pone.0025343. View

18.

Angulo J, Rouer E, Mazin A, Mattei M, Tissier A, Horellou P . Identification and expression of the cDNA of KIN17, a zinc-finger gene located on mouse chromosome 2, encoding a new DNA-binding protein. Nucleic Acids Res. 1991; 19(19):5117-23. PMC: 328864. DOI: 10.1093/nar/19.19.5117. View

19.

Zhong M, Liu Z, Wu K, Hong Z, Zhang Y, Qu J . Kin17 knockdown suppresses the migration and invasion of cervical cancer cells through NF-κB-Snail pathway. Int J Clin Exp Pathol. 2020; 13(3):607-615. PMC: 7137014. View

20.

Acloque H, Adams M, Fishwick K, Bronner-Fraser M, Nieto M . Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009; 119(6):1438-49. PMC: 2689100. DOI: 10.1172/JCI38019. View