» Articles » PMID: 28454341

The Role of FADD in Pancreatic Cancer Cell Proliferation and Drug Resistance

Overview
Journal Oncol Lett
Specialty Oncology
Date 2017 Apr 30
PMID 28454341
Citations 10
Authors
Affiliations
Soon will be listed here.
Abstract

Pancreatic cancer has one of the poorest patient outcomes and is highly resistant to chemotherapy. Identifying the molecular mechanisms involved in drug resistance is critical in the development of novel strategies to treat pancreatic cancer. The results of the present study demonstrate that Fas-associated death domain protein (FADD), a classical adaptor protein mediating apoptotic stimuli-induced cell death, protects pancreatic cancer cells from drug-induced apoptosis. In contrast to its classical apoptotic roles, it was observed that FADD is required for pancreatic cancer cell proliferation and that it is overexpressed to varying degrees in various types of pancreatic cancer cell. This leads to differing levels of drug resistance in pancreatic cancer cells, where drug resistance is positively correlated with FADD expression. Notably, the results of the present study demonstrate that FADD protects pancreatic cancer cells from drug-induced apoptosis, while RNA interference of FADD sensitizes drug-resistant cells to Adriamycin-mediated apoptosis. The results of the present study reveal unexpected roles for FADD in pancreatic cancer cell proliferation and drug resistance.

Citing Articles

Identification of PANoptosis-related biomarkers and analysis of prognostic values in head and neck squamous cell carcinoma.

Yang P, Huang G, Li Y, Yu L, Yin Z, Li Q Sci Rep. 2024; 14(1):9824.

PMID: 38684755 PMC: 11058810. DOI: 10.1038/s41598-024-60441-8.


FADD as a key molecular player in cancer progression.

Liu Y, Li X, Zhou X, Wang J, Ao X Mol Med. 2022; 28(1):132.

PMID: 36348274 PMC: 9644706. DOI: 10.1186/s10020-022-00560-y.


Heterogeneous genomic aberrations in esophageal squamous cell carcinoma: a review.

Li R, Li P, Xing W, Qiu H Am J Transl Res. 2020; 12(5):1553-1568.

PMID: 32509161 PMC: 7269976.


Knock down of Fas-Associated Protein with Death Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death.

Hollomon M, Patterson L, Santiago-OFarrill J, Kleinerman E, Gordon N J Cancer. 2020; 11(7):1657-1667.

PMID: 32194778 PMC: 7052864. DOI: 10.7150/jca.38721.


Association between ANGPTL-4 and the proinflammatory process in cancer cachexia patients.

Neto N, Boldarine V, Hachul A, Oyama L, Darck Carola Correia Lima J, Fernandez E Oncotarget. 2019; 10(60):6444-6455.

PMID: 31741709 PMC: 6849656. DOI: 10.18632/oncotarget.27269.


References
1.
King K, Cidlowski J . Cell cycle regulation and apoptosis. Annu Rev Physiol. 1998; 60:601-17. DOI: 10.1146/annurev.physiol.60.1.601. View

2.
Zhang H, Zhou X, McQuade T, Li J, Chan F, Zhang J . Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature. 2011; 471(7338):373-6. PMC: 3072026. DOI: 10.1038/nature09878. View

3.
Chinnaiyan A, ORourke K, Tewari M, Dixit V . FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 1995; 81(4):505-12. DOI: 10.1016/0092-8674(95)90071-3. View

4.
Cheng W, Wang L, Yang B, Zhang R, Yao C, He L . Self-renewal and differentiation of muscle satellite cells are regulated by the Fas-associated death domain. J Biol Chem. 2013; 289(8):5040-50. PMC: 3931063. DOI: 10.1074/jbc.M113.533448. View

5.
Zhang J, Winoto A . A mouse Fas-associated protein with homology to the human Mort1/FADD protein is essential for Fas-induced apoptosis. Mol Cell Biol. 1996; 16(6):2756-63. PMC: 231266. DOI: 10.1128/MCB.16.6.2756. View