Adams MN, Ramachandran R, Yau MK, Suen JY, Fairlie DP, Hollenberg MD, Hooper JD (2011) Structure, function and pathophysiology of protease activated receptors. Pharmacol Ther 130:248–282

Article  CAS  PubMed  Google Scholar 

Aoyagi T, Terracina KP, Raza A, Takabe K (2014) Current treatment options for colon cancer peritoneal carcinomatosis. World J Gastroenterol 20:12493–12500

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arakaki AK, Pan WA, Trejo J (2018) GPCRs in cancer: protease-activated receptors, endocytic adaptors and signaling. Int J Mol Sci 19(7):1886

Article  PubMed  PubMed Central  Google Scholar 

Babichev Y, Kabaroff L, Datti A, Uehling D, Isaac M, Al-Awar R, Prakesch M, Sun RX, Boutros PC, Venier R, Dickson BC, Gladdy RA (2016) PI3K/AKT/mTOR inhibition in combination with doxorubicin is an effective therapy for leiomyosarcoma. J Trans Med 14:67

Article  Google Scholar 

Badeanlou L, Furlan-Freguia C, Yang G, Ruf W, Samad F (2011) Tissue factor-protease-activated receptor 2 signaling promotes diet-induced obesity and adipose inflammation. Nat Med 17:1490–1497

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berg KCG, Eide PW, Eilertsen IA, Johannessen B, Bruun J, Danielsen SA, Bjornslett M, Meza-Zepeda LA, Eknaes M, Lind GE, Myklebost O, Skotheim RI, Sveen A, Lothe RA (2017) Multi-omics of 34 colorectal cancer cell lines - a resource for biomedical studies. Mol Cancer 16:116

Article  PubMed  PubMed Central  Google Scholar 

Booy EP, Henson ES, Gibson SB (2011) Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer. Oncogene 30:2367–2378

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boucher MJ, Morisset J, Vachon PH, Reed JC, Laine J, Rivard N (2000) MEK/ERK signaling pathway regulates the expression of Bcl-2, Bcl-X(L), and Mcl-1 and promotes survival of human pancreatic cancer cells. J Cell Biochem 79:355–369

Article  CAS  PubMed  Google Scholar 

Cao Z, Liao Q, Su M, Huang K, Jin J, Cao D (2019) AKT and ERK dual inhibitors: the way forward? Cancer Lett 459:30–40

Article  CAS  PubMed  Google Scholar 

Caruso R, Pallone F, Fina D, Gioia V, Peluso I, Caprioli F, Stolfi C, Perfetti A, Spagnoli LG, Palmieri G, Macdonald TT, Monteleone G (2006) Protease-activated receptor-2 activation in gastric cancer cells promotes epidermal growth factor receptor trans-activation and proliferation. Am J Pathol 169:268–278

Article  CAS  PubMed  PubMed Central  Google Scholar 

Caunt CJ, Sale MJ, Smith PD, Cook SJ (2015) MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road. Nat Rev Cancer 15:577–592

Article  CAS  PubMed  Google Scholar 

Cheng RKY, Fiez-Vandal C, Schlenker O, Edman K, Aggeler B, Brown DG, Brown GA, Cooke RM, Dumelin CE, Dore AS, Geschwindner S, Grebner C, Hermansson NO, Jazayeri A, Johansson P, Leong L, Prihandoko R, Rappas M, Soutter H, Snijder A, Sundstrom L, Tehan B, Thornton P, Troast D, Wiggin G, Zhukov A, Marshall FH, Dekker N (2017) Structural insight into allosteric modulation of protease-activated receptor 2. Nature 545:112–115

Article  CAS  PubMed  Google Scholar 

Christowitz C, Davis T, Isaacs A, van Niekerk G, Hattingh S, Engelbrecht AM (2019) Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model. BMC Cancer 19:757

Article  PubMed  PubMed Central  Google Scholar 

Consortium GT (2013) The genotype-tissue expression (GTEx) project. Nat Genet 45:580–585

Article  Google Scholar 

Darmoul D, Gratio V, Devaud H, Laburthe M (2004) Protease-activated receptor 2 in colon cancer: trypsin-induced MAPK phosphorylation and cell proliferation are mediated by epidermal growth factor receptor transactivation. J Biol Chem 279:20927–20934

Article  CAS  PubMed  Google Scholar 

Darmoul D, Marie JC, Devaud H, Gratio V, Laburthe M (2001) Initiation of human colon cancer cell proliferation by trypsin acting at protease-activated receptor-2. Br J Cancer 85:772–779

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dhanyamraju PK, Schell TD, Amin S, Robertson GP (2022) Drug-tolerant persister cells in cancer therapy resistance. Cancer Res 82:2503–2514

Article  CAS  PubMed  PubMed Central  Google Scholar 

Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B (2012) The molecular evolution of acquired resistance to targeted egfr blockade in colorectal cancers. Nature 486:537–540

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ducroc R, Bontemps C, Marazova K, Devaud H, Darmoul D, Laburthe M (2002) Trypsin is produced by and activates protease-activated receptor-2 in human cancer colon cells: evidence for new autocrine loop. Life Sci 70:1359–1367

Article  CAS  PubMed  Google Scholar 

Dutra-Oliveira A, Monteiro RQ, Mariano-Oliveira A (2012) Protease-activated receptor-2 (PAR2) mediates VEGF production through the ERK1/2 pathway in human glioblastoma cell lines. Biochem Biophys Res Commun 421:221–227

Article  CAS  PubMed  Google Scholar 

Fang XJ, Jiang H, Zhu YQ, Zhang LY, Fan QH, Tian Y (2014) Doxorubicin induces drug resistance and expression of the novel CD44st via NF-kappaB in human breast cancer MCF-7 cells. Oncol Rep 31:2735–2742

Article  CAS  PubMed  Google Scholar 

Fernando EH, Gordon MH, Beck PL, MacNaughton WK (2018) Inhibition of intestinal epithelial wound healing through protease-activated receptor-2 activation in Caco2 cells. J Pharmacol Exp Ther 367:382–392

Article  CAS  PubMed  Google Scholar 

Gewirtz DA (1999) A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 57:727–741

Article  CAS  PubMed  Google Scholar 

Goldman MJ, Craft B, Hastie M, Repecka K, McDade F, Kamath A, Banerjee A, Luo Y, Rogers D, Brooks AN, Zhu J, Haussler D (2020) Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol 38:675–678

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gores GJ, Kaufmann SH (2012) Selectively targeting Mcl-1 for the treatment of acute myelogenous Leukemia and solid tumors. Genes Dev 26:305–311

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hammond WA, Swaika A, Mody K (2016) Pharmacologic resistance in colorectal cancer: a review. Ther Adv Med Oncol 8:57–84

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heuberger DM, Schuepbach RA (2019) Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases. Thromb J 17:4

Article  PubMed  PubMed Central  Google Scholar 

Iablokov V, Hirota CL, Peplowski MA, Ramachandran R, Mihara K, Hollenberg MD, MacNaughton WK (2014) Proteinase-activated receptor 2 (PAR2) decreases apoptosis in colonic epithelial cells. J Biol Chem 289:34366–34377

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang Y, Lim J, Wu KC, Xu W, Suen JY, Fairlie DP (2021a) PAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR. Br J Pharmacol 178:913–932

Article  CAS  PubMed  Google Scholar 

Jiang Y, Yau MK, Kok WM, Lim J, Wu KC, Liu L, Hill TA, Suen JY, Fairlie DP (2017) Biased signaling by agonists of protease activated receptor 2. ACS Chem Biol 12:1217–1226

Article  CAS  PubMed  Google Scholar 

Jiang Y, Yau MK, Lim J, Wu KC, Xu W, Suen JY, Fairlie DP (2018) A potent antagonist of protease-activated receptor 2 that inhibits multiple signaling functions in human cancer cells. J Pharmacol Exp Ther 364:246–257

Article  CAS  PubMed  Google Scholar 

Jiang Y, Zhuo X, Fu X, Wu Y, Mao C (2021b) Targeting PAR2 overcomes gefitinib resistance in non-small-cell lung cancer cells through inhibition of EGFR transactivation. Front Pharmacol 12:625289

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang Y, Zhuo X, Wu Y, Fu X, Mao C (2022) PAR2 blockade reverses osimertinib resistance in non-small-cell lung cancer cells via attenuating ERK-mediated EMT and PD-L1 expression. Biochim Biophys Acta Mol Cell Res 1869:119144

Article  CAS  PubMed  Google Scholar 

Kennedy AJ, Sundstrom L, Geschwindner S, Poon EKY, Jiang Y, Chen R, Cooke R, Johnstone S, Madin A, Lim J, Liu Q, Lohman RJ, Nordqvist A, Friden-Saxin M, Yang W, Brown DG, Fairlie DP, Dekker N (2020) Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition. Commun Biol 3:782

Article  CAS  PubMed  PubMed Central