IRTKS Contributes to the Malignant Progression of Cervical Cancer Cells

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2024 Jun 13

PMID 38869721

Authors

Yan Zhang

Faping Yi

Xiaoxuan Zhang

Jing Song

Jing Cai

Jiayi Lai

Fangzhou Song

Affiliations

Soon will be listed here.

Abstract

Cervical cancer (CC), one of the most aggressive tumors in women, has high risk rates of recurrence and metastasis. It is essential to study the key genes and proteins involved in CC development. IRTKS, a member of the IRSp53 family, has been reported as a tumor promoter in gastric and breast cancers. However, the biological role of IRTKS in CC is still unclear. The purpose of this study was to explore the biological function of IRTKS in CC cells in vitro and the effect of IRTKS on tumorigenesis in vivo. Siha and Hela cells were treated with si-RNA and plasmids. Cell proliferation and growth were detected by CCK8, colony formation assay and nude mouse tumorigenicity assay, respectively. Transwell assay was used to analyze cell migration and invasion. The expression of epithelial-mesenchymal transition (EMT)-related proteins was determined by western blot. IRTKS was highly expressed in CC. IRTKS contributed to the proliferation of CC cells in vitro and in vivo. Furthermore, IRTKS facilitated the migration and invasion of CC cells and modulated EMT. IRTKS plays a crucial role in CC tumorigenesis, suggesting it may be a potential key gene for new therapeutic strategies in CC.

References

Cohen P, Jhingran A, Oaknin A, Denny L . Cervical cancer. Lancet. 2019; 393(10167):169-182. DOI: 10.1016/S0140-6736(18)32470-X. View

Vaccarella S, Franceschi S, Zaridze D, Poljak M, Veerus P, Plummer M . Preventable fractions of cervical cancer via effective screening in six Baltic, central, and eastern European countries 2017-40: a population-based study. Lancet Oncol. 2016; 17(10):1445-1452. PMC: 5052457. DOI: 10.1016/S1470-2045(16)30275-3. View

Castle P, Einstein M, Sahasrabuddhe V . Cervical cancer prevention and control in women living with human immunodeficiency virus. CA Cancer J Clin. 2021; 71(6):505-526. PMC: 10054840. DOI: 10.3322/caac.21696. View

Wang W, Jia H, Huang J, Liang Y, Tan H, Geng H . Identification of biomarkers for lymph node metastasis in early-stage cervical cancer by tissue-based proteomics. Br J Cancer. 2014; 110(7):1748-58. PMC: 3974096. DOI: 10.1038/bjc.2014.92. View

Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F . Worldwide trends in cervical cancer incidence: impact of screening against changes in disease risk factors. Eur J Cancer. 2013; 49(15):3262-73. DOI: 10.1016/j.ejca.2013.04.024. View

Hu R, Han Z, Song H, Peng Y, Huang Q, Ren S . Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. Proc Natl Acad Sci U S A. 2000; 97(17):9543-8. PMC: 16901. DOI: 10.1073/pnas.160270997. View

Scita G, Confalonieri S, Lappalainen P, Suetsugu S . IRSp53: crossing the road of membrane and actin dynamics in the formation of membrane protrusions. Trends Cell Biol. 2008; 18(2):52-60. DOI: 10.1016/j.tcb.2007.12.002. View

Millard T, Dawson J, Machesky L . Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties. J Cell Sci. 2007; 120(Pt 9):1663-72. DOI: 10.1242/jcs.001776. View

Huang L, Wang Y, Wei B, Yang J, Wang J, Wu B . Deficiency of IRTKS as an adaptor of insulin receptor leads to insulin resistance. Cell Res. 2013; 23(11):1310-21. PMC: 3817554. DOI: 10.1038/cr.2013.99. View

10.

Huang L, Wang X, Cui X, Li H, Zhao J, Wu C . IRTKS is correlated with progression and survival time of patients with gastric cancer. Gut. 2017; 67(8):1400-1409. DOI: 10.1136/gutjnl-2016-313478. View

11.

Wang Y, Huang L, Sun W, Zhang Z, Fang J, Wei B . Insulin receptor tyrosine kinase substrate activates EGFR/ERK signalling pathway and promotes cell proliferation of hepatocellular carcinoma. Cancer Lett. 2013; 337(1):96-106. DOI: 10.1016/j.canlet.2013.05.019. View

12.

Chao A, Tsai C, Jung S, Chuang W, Kao C, Hsu A . BAI1-Associated Protein 2-Like 1 (BAIAP2L1) Is a Potential Biomarker in Ovarian Cancer. PLoS One. 2015; 10(7):e0133081. PMC: 4519316. DOI: 10.1371/journal.pone.0133081. View

13.

He M, Wang Y, Cai J, Xie Y, Tao C, Jiang Y . LncRNA DLEU2 promotes cervical cancer cell proliferation by regulating cell cycle and NOTCH pathway. Exp Cell Res. 2021; 402(1):112551. DOI: 10.1016/j.yexcr.2021.112551. View

14.

Zhang X, Zhang Y, Qiu X, Cai J, Yang Z, Song F . Extracellular Vesicles Derived from Lung Cancer Cells Induce Transformation of Normal Fibroblasts into Lung Cancer-Associated Fibroblasts and Promote Metastasis of Lung Cancer by Delivering lncRNA HOTAIR. Stem Cells Int. 2022; 2022:3805013. PMC: 9578906. DOI: 10.1155/2022/3805013. View

15.

Hubbard S . The insulin receptor: both a prototypical and atypical receptor tyrosine kinase. Cold Spring Harb Perspect Biol. 2013; 5(3):a008946. PMC: 3578362. DOI: 10.1101/cshperspect.a008946. View

16.

Vingadassalom D, Kazlauskas A, Skehan B, Cheng H, Magoun L, Robbins D . Insulin receptor tyrosine kinase substrate links the E. coli O157:H7 actin assembly effectors Tir and EspF(U) during pedestal formation. Proc Natl Acad Sci U S A. 2009; 106(16):6754-9. PMC: 2672544. DOI: 10.1073/pnas.0809131106. View

17.

Lu Y, Zhou X, Zhou C, Liu J, Yong T, Fan Y . Insulin receptor tyrosine kinase substrate (IRTKS) promotes the tumorigenesis of pancreatic cancer via PI3K/AKT signaling. Hum Cell. 2022; 35(6):1885-1899. DOI: 10.1007/s13577-022-00770-w. View

18.

Deng N, Zhang X, Zhang Y . BAIAP2L1 accelerates breast cancer progression and chemoresistance by activating AKT signaling through binding with ribosomal protein L3. Cancer Sci. 2022; 114(3):764-780. PMC: 9986062. DOI: 10.1111/cas.15632. View

19.

Xu L, Du H, Zhang Q, Wang C, Yan L, Tian G . BAI1‑associated protein 2‑like 2 is a potential biomarker in lung cancer. Oncol Rep. 2018; 41(2):1304-1312. DOI: 10.3892/or.2018.6883. View

20.

Ding X, Jia X, Wang C, Xu J, Gao S, Lu C . A DHX9-lncRNA-MDM2 interaction regulates cell invasion and angiogenesis of cervical cancer. Cell Death Differ. 2018; 26(9):1750-1765. PMC: 6748089. DOI: 10.1038/s41418-018-0242-0. View