XBP1-LOX Axis is Critical in ER Stress-induced Growth of Lung Adenocarcinoma in 3D Culture

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2017 Mar 25

PMID 28337298

Citations 5

Authors

Yi Yang

Bai-Jun Cheng

Hong Jian

Zhi-Wei Chen

Yi Zhao

Yong-Feng Yu

Zi-Ming Li

Mei-Lin Liao

Shun Lu

Affiliations

Soon will be listed here.

Abstract

Rapid growth of tumor cells needs to consume large amounts of oxygen and glucose, due to lack of blood supply within the tumor, cells live in an environment that lack of oxygen and nutrients. This environment results in endoplasmic reticulum (ER) stress and activates the UPR (unfolded protein response). More and more evidence suggests UPR provides a growth signal pathway required for tumor growth. In the present study, we investigated the relationship between XBP1, one transcription factor in UPR, and the expression of LOX. We found that ER stress induces high expression of XBP1, one transcription factor in UPR, in both 2D culture and 3D culture; but only promotes growth of lung adenocarcinoma cells in in vitro 3D culture other than 2D culture. In 3D culture, we further showed that knockdown XBP1 expression can block Tm/Tg-induced cell growth. LOX genes may be key downstream effector of XBP1. Knockdown LOX expression can partially block XBP1-induced cell growth. Then we showed XBP1 suppressed by RNA interference (RNAi) can reduce the expression of LOX. For the first time, it is being shown that XBP1 can regulate the expression of LOX to promote cell growth.

Citing Articles

ROS and Endoplasmic Reticulum Stress in Pulmonary Disease.

Cui X, Zhang Y, Lu Y, Xiang M Front Pharmacol. 2022; 13:879204.

PMID: 35559240 PMC: 9086276. DOI: 10.3389/fphar.2022.879204.

The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review.

Liu Y, Mohri Z, Alsheikh W, Cheema U Cancers (Basel). 2021; 13(6).

PMID: 33809554 PMC: 7999912. DOI: 10.3390/cancers13061334.

Endoplasmic reticulum stress signals in the tumour and its microenvironment.

Chen X, Cubillos-Ruiz J Nat Rev Cancer. 2020; 21(2):71-88.

PMID: 33214692 PMC: 7927882. DOI: 10.1038/s41568-020-00312-2.

Endoplasmic Reticulum Stress in Bone Metastases.

Xu L, Zhang W, Zhang X, Chen X Front Oncol. 2020; 10:1100.

PMID: 32850317 PMC: 7396666. DOI: 10.3389/fonc.2020.01100.

Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease.

Lindholm D, Korhonen L, Eriksson O, Koks S Front Cell Dev Biol. 2017; 5:48.

PMID: 28540288 PMC: 5423914. DOI: 10.3389/fcell.2017.00048.

References

Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, Hu N . ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J. 2005; 24(19):3470-81. PMC: 1276162. DOI: 10.1038/sj.emboj.7600777. View

Stassar M, Devitt G, BROSIUS M, Rinnab L, Prang J, Schradin T . Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer. 2001; 85(9):1372-82. PMC: 2375251. DOI: 10.1054/bjoc.2001.2074. View

Erler J, Bennewith K, Nicolau M, Dornhofer N, Kong C, Le Q . Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 2006; 440(7088):1222-6. DOI: 10.1038/nature04695. View

Kirschmann D, Seftor E, Nieva D, Mariano E, Hendrix M . Differentially expressed genes associated with the metastatic phenotype in breast cancer. Breast Cancer Res Treat. 1999; 55(2):127-36. DOI: 10.1023/a:1006188129423. View

Chan S, Egan P . Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response. FASEB J. 2005; 19(11):1510-2. DOI: 10.1096/fj.04-3455fje. View

Meads M, Gatenby R, Dalton W . Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer. 2009; 9(9):665-74. DOI: 10.1038/nrc2714. View

Romero-Ramirez L, Cao H, Nelson D, Hammond E, Lee A, Yoshida H . XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Res. 2004; 64(17):5943-7. DOI: 10.1158/0008-5472.CAN-04-1606. View

Rodriguez C, Martinez-Gonzalez J, Raposo B, Alcudia J, Guadall A, Badimon L . Regulation of lysyl oxidase in vascular cells: lysyl oxidase as a new player in cardiovascular diseases. Cardiovasc Res. 2008; 79(1):7-13. DOI: 10.1093/cvr/cvn102. View

Romero-Ramirez L, Cao H, Regalado M, Kambham N, Siemann D, Kim J . X box-binding protein 1 regulates angiogenesis in human pancreatic adenocarcinomas. Transl Oncol. 2009; 2(1):31-8. PMC: 2647700. DOI: 10.1593/tlo.08211. View

10.

Ganley I, Wong P, Gammoh N, Jiang X . Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest. Mol Cell. 2011; 42(6):731-43. PMC: 3124681. DOI: 10.1016/j.molcel.2011.04.024. View

11.

Sasser A, Mundy B, Smith K, Studebaker A, Axel A, Haidet A . Human bone marrow stromal cells enhance breast cancer cell growth rates in a cell line-dependent manner when evaluated in 3D tumor environments. Cancer Lett. 2007; 254(2):255-64. DOI: 10.1016/j.canlet.2007.03.012. View

12.

Payne S, Hendrix M, Kirschmann D . Paradoxical roles for lysyl oxidases in cancer--a prospect. J Cell Biochem. 2007; 101(6):1338-54. DOI: 10.1002/jcb.21371. View

13.

Boelens J, Lust S, Offner F, Bracke M, Vanhoecke B . Review. The endoplasmic reticulum: a target for new anticancer drugs. In Vivo. 2007; 21(2):215-26. View

14.

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

15.

Friedrich J, Seidel C, Ebner R, Kunz-Schughart L . Spheroid-based drug screen: considerations and practical approach. Nat Protoc. 2009; 4(3):309-24. DOI: 10.1038/nprot.2008.226. View

16.

Kirschmann D, Seftor E, Fong S, Nieva D, Sullivan C, Edwards E . A molecular role for lysyl oxidase in breast cancer invasion. Cancer Res. 2002; 62(15):4478-83. View

17.

Chen Y, Feldman D, Deng C, Brown J, De Giacomo A, Gaw A . Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae. Mol Cancer Res. 2005; 3(12):669-77. DOI: 10.1158/1541-7786.MCR-05-0181. View

18.

Weigelt B, Bissell M . Unraveling the microenvironmental influences on the normal mammary gland and breast cancer. Semin Cancer Biol. 2008; 18(5):311-21. PMC: 2548304. DOI: 10.1016/j.semcancer.2008.03.013. View