FAM83A is Amplified and Promotes Cancer Stem Cell-like Traits and Chemoresistance in Pancreatic Cancer

Overview

Journal Oncogenesis

Date 2017 Mar 14

PMID 28287611

Citations 52

Authors

S Chen

J Huang

Z Liu

Q Liang

N Zhang

Y Jin

Affiliations

Soon will be listed here.

Abstract

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. In the current study, we found family with sequence similarity 83, member A (FAM83A) is significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, CSC-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. Furthermore, overexpression of FAM83A activated the well-characterized CSC-associated pathways transforming growth factor-β (TGF-β) signaling and Wnt/β-catenin signaling. Importantly, the FAM83A locus was amplified in a number of human cancers and silencing FAM83A in associated cancer cell lines inhibited activation of the WNT/β-catenin and TGF-β signaling pathways and reduced tumorigenicity. Taken together, these results indicate that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target.

Citing Articles

Promotion of stem cell-like phenotype of lung adenocarcinoma by FAM83A via stabilization of ErbB2.

Yuan Y, Hao L, Huang J, Zhao F, Ju Y, Wang J Cell Death Dis. 2024; 15(6):460.

PMID: 38942760 PMC: 11213963. DOI: 10.1038/s41419-024-06853-w.

Diagnostic value of immune-related biomarker FAM83A in differentiating malignant from benign pleural effusion in lung adenocarcinoma.

Liu H, Yao J, Liu Y, Wu L, Tan Z, Hu J Discov Oncol. 2024; 15(1):242.

PMID: 38914812 PMC: 11196556. DOI: 10.1007/s12672-024-01109-7.

Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma.

Gan J, Huang M, Wang W, Fu G, Hu M, Zhong H J Transl Med. 2024; 22(1):428.

PMID: 38711158 PMC: 11075300. DOI: 10.1186/s12967-024-05146-2.

Integrated single-cell and bulk RNA sequencing in pancreatic cancer identifies disulfidptosis-associated molecular subtypes and prognostic signature.

Wu Y, Shang J, Ruan Q, Tan X Sci Rep. 2023; 13(1):17577.

PMID: 37845218 PMC: 10579418. DOI: 10.1038/s41598-023-43036-7.

Genomic analysis and filtration of novel prognostic biomarkers based on metabolic and immune subtypes in pancreatic cancer.

Chen G, Liu Y, Su D, Qiu J, Long J, Zhao F Cell Oncol (Dordr). 2023; 46(6):1691-1708.

PMID: 37434012 DOI: 10.1007/s13402-023-00836-3.

References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Mishra L, Derynck R, Mishra B . Transforming growth factor-beta signaling in stem cells and cancer. Science. 2005; 310(5745):68-71. DOI: 10.1126/science.1118389. View

Singh S, Chen N, Hessmann E, Siveke J, Lahmann M, Singh G . Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity. EMBO J. 2015; 34(4):517-30. PMC: 4331005. DOI: 10.15252/embj.201489574. View

Lee S, Heinrich E, Lu J, Lee W, Choi A, Luu C . Epidermal Growth Factor Receptor Signaling to the Mitogen Activated Protein Kinase Pathway Bypasses Ras in Pancreatic Cancer Cells. Pancreas. 2015; 45(2):286-92. PMC: 5891223. DOI: 10.1097/MPA.0000000000000379. View

Jimeno A, Feldmann G, Suarez-Gauthier A, Rasheed Z, Solomon A, Zou G . A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol Cancer Ther. 2009; 8(2):310-4. PMC: 3033101. DOI: 10.1158/1535-7163.MCT-08-0924. View

Jin L, Hope K, Zhai Q, Smadja-Joffe F, Dick J . Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006; 12(10):1167-74. DOI: 10.1038/nm1483. View

Goode E, Chenevix-Trench G, Song H, Ramus S, Notaridou M, Lawrenson K . A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet. 2010; 42(10):874-9. PMC: 3020231. DOI: 10.1038/ng.668. View

Liu S, Dontu G, Mantle I, Patel S, Ahn N, Jackson K . Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006; 66(12):6063-71. PMC: 4386278. DOI: 10.1158/0008-5472.CAN-06-0054. View

Li J, Wientjes M, Au J . Pancreatic cancer: pathobiology, treatment options, and drug delivery. AAPS J. 2010; 12(2):223-32. PMC: 2844509. DOI: 10.1208/s12248-010-9181-5. View

10.

Dean M, Fojo T, Bates S . Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5(4):275-84. DOI: 10.1038/nrc1590. View

11.

Yamaguchi H, Kojima T, Ito T, Kimura Y, Imamura M, Son S . Transcriptional control of tight junction proteins via a protein kinase C signal pathway in human telomerase reverse transcriptase-transfected human pancreatic duct epithelial cells. Am J Pathol. 2010; 177(2):698-712. PMC: 2913360. DOI: 10.2353/ajpath.2010.091226. View

12.

Tan A, Alexe G, Reiss M . Transforming growth factor-beta signaling: emerging stem cell target in metastatic breast cancer?. Breast Cancer Res Treat. 2008; 115(3):453-95. PMC: 2693232. DOI: 10.1007/s10549-008-0184-1. View

13.

Liu L, Ma C, Xu Q, Cheng L, Xiao L, Xu D . A rapid nested polymerase chain reaction method to detect circulating cancer cells in breast cancer patients using multiple marker genes. Oncol Lett. 2014; 7(6):2192-2198. PMC: 4049700. DOI: 10.3892/ol.2014.2048. View

14.

Clevers H . The cancer stem cell: premises, promises and challenges. Nat Med. 2011; 17(3):313-9. DOI: 10.1038/nm.2304. View

15.

Sachlos E, Risueno R, Laronde S, Shapovalova Z, Lee J, Russell J . Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells. Cell. 2012; 149(6):1284-97. DOI: 10.1016/j.cell.2012.03.049. View

16.

Hermann P, Huber S, Herrler T, Aicher A, Ellwart J, Guba M . Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2008; 1(3):313-23. DOI: 10.1016/j.stem.2007.06.002. View

17.

McAuliffe S, Morgan S, Wyant G, Tran L, Muto K, Chen Y . Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc Natl Acad Sci U S A. 2012; 109(43):E2939-48. PMC: 3491453. DOI: 10.1073/pnas.1206400109. View

18.

Pattabiraman D, Weinberg R . Tackling the cancer stem cells - what challenges do they pose?. Nat Rev Drug Discov. 2014; 13(7):497-512. PMC: 4234172. DOI: 10.1038/nrd4253. View

19.

Liu L, Liao G, He P, Zhu H, Liu P, Qu Y . Detection of circulating cancer cells in lung cancer patients with a panel of marker genes. Biochem Biophys Res Commun. 2008; 372(4):756-60. DOI: 10.1016/j.bbrc.2008.05.101. View

20.

Tseng Y, Moriarity B, Gong W, Akiyama R, Tiwari A, Kawakami H . PVT1 dependence in cancer with MYC copy-number increase. Nature. 2014; 512(7512):82-6. PMC: 4767149. DOI: 10.1038/nature13311. View