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Hypoxic activation of the PERK/eIF2α arm of the unfolded protein response promotes metastasis through induction of LAMP3.

Mujcic H, Nagelkerke A, Rouschop KM, Chung S, Chaudary N, Span PN, Clarke B, Milosevic M, Sykes J, Hill RP, Koritzinsky M, Wouters BG.

Clin Cancer Res. 2013 Nov 15;19(22):6126-37. doi: 10.1158/1078-0432.CCR-13-0526. Epub 2013 Sep 17.


PERK/eIF2α signaling protects therapy resistant hypoxic cells through induction of glutathione synthesis and protection against ROS.

Rouschop KM, Dubois LJ, Keulers TG, van den Beucken T, Lambin P, Bussink J, van der Kogel AJ, Koritzinsky M, Wouters BG.

Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4622-7. doi: 10.1073/pnas.1210633110. Epub 2013 Mar 7.


The PERK/ATF4/LAMP3-arm of the unfolded protein response affects radioresistance by interfering with the DNA damage response.

Nagelkerke A, Bussink J, van der Kogel AJ, Sweep FC, Span PN.

Radiother Oncol. 2013 Sep;108(3):415-21. doi: 10.1016/j.radonc.2013.06.037. Epub 2013 Jul 25.


Hypoxic activation of the unfolded protein response (UPR) induces expression of the metastasis-associated gene LAMP3.

Mujcic H, Rzymski T, Rouschop KM, Koritzinsky M, Milani M, Harris AL, Wouters BG.

Radiother Oncol. 2009 Sep;92(3):450-9. doi: 10.1016/j.radonc.2009.08.017. Epub 2009 Aug 31.


Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer.

Kanao H, Enomoto T, Kimura T, Fujita M, Nakashima R, Ueda Y, Ueno Y, Miyatake T, Yoshizaki T, Buzard GS, Tanigami A, Yoshino K, Murata Y.

Cancer Res. 2005 Oct 1;65(19):8640-5.


Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer.

Nagelkerke A, Mujcic H, Bussink J, Wouters BG, van Laarhoven HW, Sweep FC, Span PN.

Cancer. 2011 Aug 15;117(16):3670-81. doi: 10.1002/cncr.25938. Epub 2011 Feb 11.


Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response.

Nagelkerke A, Bussink J, Mujcic H, Wouters BG, Lehmann S, Sweep FC, Span PN.

Breast Cancer Res. 2013 Jan 7;15(1):R2. doi: 10.1186/bcr3373.


Hypoxic regulation of the PERK/ATF4/LAMP3-arm of the unfolded protein response in head and neck squamous cell carcinoma.

Nagelkerke A, Sweep FC, Stegeman H, Grénman R, Kaanders JH, Bussink J, Span PN.

Head Neck. 2014 Mar 14. doi: 10.1002/hed.23693. [Epub ahead of print]


The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth.

Fels DR, Koumenis C.

Cancer Biol Ther. 2006 Jul;5(7):723-8. Epub 2006 Jul 1. Review.


Modulation of the Akt pathway reveals a novel link with PERK/eIF2α, which is relevant during hypoxia.

Blaustein M, Pérez-Munizaga D, Sánchez MA, Urrutia C, Grande A, Risso G, Srebrow A, Alfaro J, Colman-Lerner A.

PLoS One. 2013 Jul 29;8(7):e69668. doi: 10.1371/journal.pone.0069668. Print 2013.


Increased expression of metastasis-related genes in hypoxic cells sorted from cervical and lymph nodal xenograft tumors.

Chaudary N, Hill RP.

Lab Invest. 2009 May;89(5):587-96. doi: 10.1038/labinvest.2009.16. Epub 2009 Mar 23.


The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5.

Rouschop KM, van den Beucken T, Dubois L, Niessen H, Bussink J, Savelkouls K, Keulers T, Mujcic H, Landuyt W, Voncken JW, Lambin P, van der Kogel AJ, Koritzinsky M, Wouters BG.

J Clin Invest. 2010 Jan;120(1):127-41. doi: 10.1172/JCI40027. Epub 2009 Dec 14.


Activating transcription factor 4 is translationally regulated by hypoxic stress.

Blais JD, Filipenko V, Bi M, Harding HP, Ron D, Koumenis C, Wouters BG, Bell JC.

Mol Cell Biol. 2004 Sep;24(17):7469-82.


New small molecule inhibitors of UPR activation demonstrate that PERK, but not IRE1α signaling is essential for promoting adaptation and survival to hypoxia.

Cojocari D, Vellanki RN, Sit B, Uehling D, Koritzinsky M, Wouters BG.

Radiother Oncol. 2013 Sep;108(3):541-7. doi: 10.1016/j.radonc.2013.06.005. Epub 2013 Jul 3.


Hypoxia-induced expression of carbonic anhydrase 9 is dependent on the unfolded protein response.

van den Beucken T, Koritzinsky M, Niessen H, Dubois L, Savelkouls K, Mujcic H, Jutten B, Kopacek J, Pastorekova S, van der Kogel AJ, Lambin P, Voncken W, Rouschop KM, Wouters BG.

J Biol Chem. 2009 Sep 4;284(36):24204-12. doi: 10.1074/jbc.M109.006510. Epub 2009 Jun 29.


Novel metastasis-related gene CIM functions in the regulation of multiple cellular stress-response pathways.

Yanagisawa K, Konishi H, Arima C, Tomida S, Takeuchi T, Shimada Y, Yatabe Y, Mitsudomi T, Osada H, Takahashi T.

Cancer Res. 2010 Dec 1;70(23):9949-58. doi: 10.1158/0008-5472.CAN-10-1055. Epub 2010 Nov 30.


Hypoxia signaling and the metastatic phenotype.

Mujcic H, Hill RP, Koritzinsky M, Wouters BG.

Curr Mol Med. 2014;14(5):565-79. Review.


ER stress, hypoxia tolerance and tumor progression.

Koumenis C.

Curr Mol Med. 2006 Feb;6(1):55-69. Review.


Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha.

Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, Koromilas A, Wouters BG.

Mol Cell Biol. 2002 Nov;22(21):7405-16.


6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress.

Hu R, Zhou P, Peng YB, Xu X, Ma J, Liu Q, Zhang L, Wen XD, Qi LW, Gao N, Li P.

PLoS One. 2012;7(6):e39664. doi: 10.1371/journal.pone.0039664. Epub 2012 Jun 29.

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