Effects of TWEAK/Fn14 pathway on the process of cell proliferation in pancreatic cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GUO Qiang ¹ , WEI Ailin ² ,  GONG Shu ²

1. Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R.China;
2. Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R.China;

Corresponding author：

GONG Shu, Email: gdy-29@163.com

Keywords：

TNF-related weak inducer of apoptosis; fibroblast growth factor-inducible 14; pancreatic cancer; RNA interference

DOI：

10.7507/1007-9424.201609015

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of TNF-related weak inducer of apoptosis/fibroblast growth Factor-inducible 14 (TWEAK/Fn14) on the cell proliferation by transfecting Fn14 shRNA to PANC-1 cells. Methods The shRNA gene targeting Fn14 gene was constructed and transfected into pancreatic cancer cell line PANC-1 to specifically silence the expression of Fn14 gene. The effect of shRNA interference sequence on the expression of Fn14 was detected by flow cytometry and immunofluorescence. CCK-8 was used to detect the cell proliferation of PANC-1 after blocking TWEAK-induced signal pathway. Western blotting method was used to detect the expressions of downstream factors such as nuclear factor-kappa B (NF-κB), TWEAK and caspase-3 to explore the pathway mechanism of TWEAK/Fn14. Results The absorbance value (A value) in the Fn14 shRNA group was significantly lower than the control groups in 24 hours after transfected (P<0.000 1). After the specific shRNA sequences transfected PANC-1 cells, NF-κB, TWEAK and caspase-3 protein expressions were also significantly lower than the control group (P<0.05), and the apoptosis of PANC-1 cells increased after inhibition of TWEAK/Fn14 signaling pathway. Conclusions TWEAK/Fn14 involved in the progression of pancreatic cancer. The Fn14 expression could influence the process of cell apoptosis.

Citation： GUO Qiang, WEI Ailin, GONG Shu. Effects of TWEAK/Fn14 pathway on the process of cell proliferation in pancreatic cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(4): 432-437. doi: 10.7507/1007-9424.201609015 Copy

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5.	Chicheportiche Y, Bourdon PR, Xu H,et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem, 1997, 272(51): 32401-32410.
6.	Bossen C, Tardivel A, Bodmer JL,et al. Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human. J Bio Chem, 2006, 281(20): 13964-13971.
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9.	Cao Y. Antiangiogenic cancer therapy. Semin Cancer Biol, 2004, 14(2): 139-145.
10.	Sun SC. Non-canonical NF-κB signaling pathway. Cell Res, 2011, 21(1): 71-85.
11.	Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer, 2013, 12(1): 86.
12.	Kwon OH, Kim JH, Kim SY,et al. TWEAK/Fn14 signaling mediates gastric cancer cell resistance to 5-fluorouracil via NF-κB activation. Int J Oncol, 2014, 44(2): 583-590.
13.	Chen HN, Wang DJ, Ren MY,et al.TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-кB pathway. Mol Biol Rep, 2012, 39(8): 8231-8241.
14.	Li X, Li Y, Wang B,et al. Delivery of the co-expression plasmid pEndo-Si-Stat3 by attenuated Salmonella serovar typhimurium for prostate cancer treatment. J Cancer Res Clin Oncol, 2013: 139(6): 971-980.
15.	Kuribayashi K, Mayes PA, El-Deiry WS. What are caspases 3 and 7 doing upstream of the mitochondria? Cancer Biol Ther, 2006, 5(7): 763-765.
16.	Wang D, Fung JN, Tuo Y,et al. TWEAK/Fn14 promotes apoptosis of human endometrial cancer cells via caspase pathway. Cancer Lett, 2010, 294(1): 91-100.
17.	Pettersen I, Baryawno N, Abel F,et al. Expression of TWEAK/Fn14 in neuroblastoma: implications in tumorigenesis. Int J Oncol, 2013, 42(4): 1239-1248.
18.	Kawakita T, Yamanaka Y, Yamaguchi Y,et al. Functional expression of TWEAK in human hepatocellular carcinoma: possible implication in cell proliferation and tumor angiogenesis. Biochem Biophys Res Commun, 2004, 318(3): 726-733.
19.	Zhao H, Langerød A, Y Ji,et al. Different gene expression patterns in invasive lobular and ductal carcinomas of the breast. Mol Biol Cell, 2004, 15(6): 2523-2536.
20.	Gu L, Dai L, Cao C,et al. Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention. PLoS One, 2013, 8(3): e57436.
21.	Zou H, Wang D, Gan X,et al. Low TWEAK expression is correlated to the progression of squamous cervical carcinoma. Gynecol Oncol, 2011, 123(1): 123-128.
22.	Burkly LC, Zheng TS. TWEAK/Fn14 pathway: an immunological switch for shaping tissue responses. Immunol Rev, 2011, 244(1): 99-114.
23.	Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov, 2008, 7(5): 11-25.
24.	Burkly LC, Dohi T. The TWEAK/Fn14 pathway in tissue remodeling: for better or for worse. Adv Exp Med Biol, 2011, 691: 305-322.
25.	Dohi T, LC Burkly. TWEAK/Fn14 pathway as an aggravating and perpetuating factor in inflammatory diseases: focus on inflammatory bowel diseases. J Leukoc Biol, 2012, 92(2): 265-279.

1. Chen W, Zheng R, Baade PD,et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2. Vauthey JN, Dixon E. AHPBA/SSO/SSAT Consensus Conference on Resectable and Borderline Resectable Pancreatic Cancer: rationale and overview of the conference. Ann Surg Oncol, 2009, 16(7): 1725-1726.
3. Bliss LA, Witkowski ER, Yang CJ,et al. Outcomes in operative management of pancreatic cancer. J Surg Oncol, 2014, 110(5): 592-598.
4. Konstantinidis IT, Warshaw AL, Allen JN,et al. Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a " true” R0 resection? Ann Surg, 2013, 257(4): 731-736.
5. Chicheportiche Y, Bourdon PR, Xu H,et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem, 1997, 272(51): 32401-32410.
6. Bossen C, Tardivel A, Bodmer JL,et al. Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human. J Bio Chem, 2006, 281(20): 13964-13971.
7. Bergers G. Tumorigenesis and the angiogenic switch. Nat Rev Cancer, 2003, 3(6): 401-410.
8. Tonini T, Rossi F, Claudio PP. Molecular basis of angiogenesis and cancer. Oncogene, 2003, 22(42): 6549-6556.
9. Cao Y. Antiangiogenic cancer therapy. Semin Cancer Biol, 2004, 14(2): 139-145.
10. Sun SC. Non-canonical NF-κB signaling pathway. Cell Res, 2011, 21(1): 71-85.
11. Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer, 2013, 12(1): 86.
12. Kwon OH, Kim JH, Kim SY,et al. TWEAK/Fn14 signaling mediates gastric cancer cell resistance to 5-fluorouracil via NF-κB activation. Int J Oncol, 2014, 44(2): 583-590.
13. Chen HN, Wang DJ, Ren MY,et al.TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-кB pathway. Mol Biol Rep, 2012, 39(8): 8231-8241.
14. Li X, Li Y, Wang B,et al. Delivery of the co-expression plasmid pEndo-Si-Stat3 by attenuated Salmonella serovar typhimurium for prostate cancer treatment. J Cancer Res Clin Oncol, 2013: 139(6): 971-980.
15. Kuribayashi K, Mayes PA, El-Deiry WS. What are caspases 3 and 7 doing upstream of the mitochondria? Cancer Biol Ther, 2006, 5(7): 763-765.
16. Wang D, Fung JN, Tuo Y,et al. TWEAK/Fn14 promotes apoptosis of human endometrial cancer cells via caspase pathway. Cancer Lett, 2010, 294(1): 91-100.
17. Pettersen I, Baryawno N, Abel F,et al. Expression of TWEAK/Fn14 in neuroblastoma: implications in tumorigenesis. Int J Oncol, 2013, 42(4): 1239-1248.
18. Kawakita T, Yamanaka Y, Yamaguchi Y,et al. Functional expression of TWEAK in human hepatocellular carcinoma: possible implication in cell proliferation and tumor angiogenesis. Biochem Biophys Res Commun, 2004, 318(3): 726-733.
19. Zhao H, Langerød A, Y Ji,et al. Different gene expression patterns in invasive lobular and ductal carcinomas of the breast. Mol Biol Cell, 2004, 15(6): 2523-2536.
20. Gu L, Dai L, Cao C,et al. Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention. PLoS One, 2013, 8(3): e57436.
21. Zou H, Wang D, Gan X,et al. Low TWEAK expression is correlated to the progression of squamous cervical carcinoma. Gynecol Oncol, 2011, 123(1): 123-128.
22. Burkly LC, Zheng TS. TWEAK/Fn14 pathway: an immunological switch for shaping tissue responses. Immunol Rev, 2011, 244(1): 99-114.
23. Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov, 2008, 7(5): 11-25.
24. Burkly LC, Dohi T. The TWEAK/Fn14 pathway in tissue remodeling: for better or for worse. Adv Exp Med Biol, 2011, 691: 305-322.
25. Dohi T, LC Burkly. TWEAK/Fn14 pathway as an aggravating and perpetuating factor in inflammatory diseases: focus on inflammatory bowel diseases. J Leukoc Biol, 2012, 92(2): 265-279.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of TWEAK/Fn14 pathway on the process of cell proliferation in pancreatic cancer

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