Tumor Suppressive Effect of Scavenger Receptor Class A Member 5 Overexpression in Colorectal Cancer by Regulating PI3K/AKT/mTOR Pathway

Overview

Journal Genes Genomics

Specialty Genetics

Date 2021 Aug 21

PMID 34417976

Citations 4

Authors

Yi Li

Feng Peng

Xiangyun Tan

Jin Wang

Yeqing Xu

Affiliations

Soon will be listed here.

Abstract

Background: Colorectal cancer (CRC) exhibits high risks of morbidity and mortality.

Objective: To investigate the effect of scavenger receptor class A member 5 (SCRAR5) on CRC and its mechanism on modulation of cancer development.

Methods: The SCRAR5 expression in four kinds of CRC cell lines (SW620, SW480, HT29, and HCT116) was measured by quantitative PCR and western blotting, respectively. The effects of SCRAR5 abnormal expression on cell proliferation, apoptosis, and migration were analyzed by CCK-8 assay, EdU assay, colony-forming assay, flow cytometry assay, Transwell assay and wound healing assay, respectively. Meanwhile, the involvements of PI3K/AKT/mTOR pathway with the role of SCRAR5 were investigated by western blotting. Afterwards, the in vivo effects of SCRAR5 abnormal expression on CRC xenograft mice were finally investigated by evaluating tumor volume, apoptosis and Ki67 expression.

Results: SCRAR5 was lowly expressed in CRC cell lines, especially SW480 cells. Up-regulation of SCRAR5 significantly promoted cell apoptosis, reduced cell proliferation and migration in SW480 cells. Notably, SCRAR5 overexpression obviously inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Reversely, SCRAR5 silence exhibited promoting effects on HT29 cells. Consistently, in vivo experiments also revealed that SCRAR5 overexpression remarkably suppressed tumor volume and Ki67 expression, as well as promoted cell apoptosis.

Conclusions: Overall, up-regulating of SCRAR5 obviously inhibited CRC tumor growth in vitro and in vivo, which might be related to PI3K/AKT/mTOR pathway.

Citing Articles

Crumbling Pathogenesis and Biomarkers for Diabetic Peripheral Neuropathy.

Chong Z, Souayah N Biomedicines. 2025; 13(2).

PMID: 40002826 PMC: 11853266. DOI: 10.3390/biomedicines13020413.

The Role of SCARA5 as a Potential Biomarker in Squamous Cell Carcinoma of the Lung.

Flockerzi F, Hohneck J, Langer F, Trankenschuh W, Stahl P Int J Mol Sci. 2024; 25(13).

PMID: 39000462 PMC: 11242384. DOI: 10.3390/ijms25137355.

Paeonol upregulates expression of tumor suppressors TNNC1 and SCARA5, exerting anti-tumor activity in non-small cell lung cancer cells.

Zhang C, Zhang J, Guo K Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(7):5241-5251.

PMID: 38265681 DOI: 10.1007/s00210-024-02963-6.

SCARA5 Is Overexpressed in Prostate Cancer and Linked to Poor Prognosis.

Flockerzi F, Hohneck J, Saar M, Bohle R, Stahl P Diagnostics (Basel). 2023; 13(13).

PMID: 37443605 PMC: 10340403. DOI: 10.3390/diagnostics13132211.

SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways.

Huang J, Lv C, Zhao B, Ji Z, Gao Z Open Med (Wars). 2023; 18(1):20230627.

PMID: 36785765 PMC: 9921916. DOI: 10.1515/med-2023-0627.

References

Yan N, Zhang S, Yang Y, Cheng L, Li C, Dai L . Therapeutic upregulation of Class A scavenger receptor member 5 inhibits tumor growth and metastasis. Cancer Sci. 2012; 103(9):1631-9. PMC: 7659270. DOI: 10.1111/j.1349-7006.2012.02350.x. View

PrabhuDas M, Baldwin C, Bollyky P, Bowdish D, Drickamer K, Febbraio M . A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease. J Immunol. 2017; 198(10):3775-3789. PMC: 5671342. DOI: 10.4049/jimmunol.1700373. View

Shukla H . Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer. Proteomes. 2017; 5(4). PMC: 5748563. DOI: 10.3390/proteomes5040028. View

Keum N, Giovannucci E . Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019; 16(12):713-732. DOI: 10.1038/s41575-019-0189-8. View

Liu J, Hu G, Chen D, Gong A, Soori G, Dobleman T . Suppression of SCARA5 by Snail1 is essential for EMT-associated cell migration of A549 cells. Oncogenesis. 2013; 2:e73. PMC: 3816226. DOI: 10.1038/oncsis.2013.37. View

Porta C, Paglino C, Mosca A . Targeting PI3K/Akt/mTOR Signaling in Cancer. Front Oncol. 2014; 4:64. PMC: 3995050. DOI: 10.3389/fonc.2014.00064. View

Pluddemann A, Neyen C, Gordon S . Macrophage scavenger receptors and host-derived ligands. Methods. 2007; 43(3):207-17. DOI: 10.1016/j.ymeth.2007.06.004. View

Siegel R, Miller K, Sauer A, Fedewa S, Butterly L, Anderson J . Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020; 70(3):145-164. DOI: 10.3322/caac.21601. View

Yu B, Cheng C, Wu Y, Guo L, Kong D, Zhang Z . Interactions of ferritin with scavenger receptor class A members. J Biol Chem. 2020; 295(46):15727-15741. PMC: 7667961. DOI: 10.1074/jbc.RA120.014690. View

10.

Rejhova A, Opattova A, cumova A, Sliva D, Vodicka P . Natural compounds and combination therapy in colorectal cancer treatment. Eur J Med Chem. 2018; 144:582-594. DOI: 10.1016/j.ejmech.2017.12.039. View

11.

Noorolyai S, Shajari N, Baghbani E, Sadreddini S, Baradaran B . The relation between PI3K/AKT signalling pathway and cancer. Gene. 2019; 698:120-128. DOI: 10.1016/j.gene.2019.02.076. View

12.

Liu Y, Tan Y, Sun W, Ju W, Fu Y, Wang L . Identification of SCARA5 as a Potential Biomarker for Oral Squamous Cell Carcinoma using MALDI-TOF-MS Analysis. Proteomics Clin Appl. 2018; 12(5):e1700180. DOI: 10.1002/prca.201700180. View

13.

Polivka Jr J, Janku F . Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 2013; 142(2):164-75. DOI: 10.1016/j.pharmthera.2013.12.004. View

14.

Wang S, Zhou D, Xu Z, Song J, Qian X, Lv X . Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect. Curr Drug Targets. 2019; 20(11):1180-1202. DOI: 10.2174/1389450120666190402145325. View

15.

Whelan F, Meehan C, Golding G, McConkey B, Bowdish D . The evolution of the class A scavenger receptors. BMC Evol Biol. 2012; 12:227. PMC: 3567963. DOI: 10.1186/1471-2148-12-227. View

16.

Liu J, Zeng M, Shi P, Cao Y, Zhang J, Xie Y . SCARA5 is a Novel Biomarker in Colorectal Cancer by Comprehensive Analysis. Clin Lab. 2020; 66(7). DOI: 10.7754/Clin.Lab.2019.191015. View

17.

Xue J, Jin X, Wan X, Yin X, Fang M, Liu T . Effects and Mechanism of Tanshinone II A in Proliferation, Apoptosis, and Migration of Human Colon Cancer Cells. Med Sci Monit. 2019; 25:4793-4800. PMC: 6612241. DOI: 10.12659/MSM.914446. View

18.

Liu H, Hu J, Pan H, Luo D, Huang M, Xu W . CSN5 Promotes Hepatocellular Carcinoma Progression by SCARA5 Inhibition Through Suppressing β-Catenin Ubiquitination. Dig Dis Sci. 2017; 63(1):155-165. DOI: 10.1007/s10620-017-4855-9. View

19.

You K, Su F, Liu L, Lv X, Zhang J, Zhang Y . SCARA5 plays a critical role in the progression and metastasis of breast cancer by inactivating the ERK1/2, STAT3, and AKT signaling pathways. Mol Cell Biochem. 2017; 435(1-2):47-58. DOI: 10.1007/s11010-017-3055-4. View

20.

Marmol I, Sanchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi M . Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017; 18(1). PMC: 5297828. DOI: 10.3390/ijms18010197. View