Colorectal cancer and endoplasmic reticulum stress – potential targets for therapeutic compounds
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Universidade Federal de Mato Grosso do Sul, Brazil
Instituto de Assistência a Pesquisa em Educação e Saúde (IAPES), Brazil
Corresponding author
Almir Sousa Martins   

Universidade Federal de Mato Grosso do Sul, Av Costa e Silva (S/N), 79070–900, Campo Grande-MS, Brazi
J Pre Clin Clin Res. 2024;1(18):54-66
Introduction and objective:
Colorectal cancer (CRC), a malignant neoplasm of the gastrointestinal tract, affects the colon and rectum, its incidence is high, being the third most common neoplasm in men, with two million cases/year and survival <70%/5 years. The pathophysiology and progression of CRC are closely related to endoplasmic reticulum stress (ERE) and the unfolded or misfolded protein response (UPR). ERE can be triggered by various oxidative stress and inflammation factors with high UPR load followed by physicochemical and conformational interactions. The aim of the review is to present recent evidence on the relationships between endoplasmic reticulum stress, unfolded protein response and colorectal cancer.

Review methods:
An expanded integrative review was carried out of scientific information from PubMed, LILACS and SciELO health databases. Articles containing key words were selected for abstract fast readings, followed by full text selections of works containing targeted subjects. From a total of 198 articles, 96 were selected (92% ≤ 8 years) for inclusion in the review.

Brief description of the state of knowledge:
New developments in CRC research are presented within approaches to molecular pathophysiological pathways, a spectrum of therapeutic targets and suggestive diets with a view of intestinal microbiota and dysbiosis, considering progression stages and evidences correlating CRC to socio-environmental and innate or acquired genetic load. Putative CRC target compounds and drugs, such as Aspirin, Fucoidan, PERK inhibitor, antimicrobial and current natural antioxidants are briefly presented and discussed.

Chaperone proteins may accumulate misfolded proteins in the endoplasmic reticulum, causing disruption of ERE proteostasis. While CRC progression is closely related to these signaling pathways, a better understanding is vital for new target-specific anticarcinogenic molecules.

Mattiuzzi C, Sanchis-Gomar F, Lippi G. Concise update on colorectal cancer epidemiology. Ann Transl Med. 2019;7(21):609. https://doi. org/10.21037/atm.2019.07.91.
Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73(3):233–254. https://doi. org/10.3322/caac.21772.
Lewandowska A, Rudzki G, Lewandowski T, Stryjkowska- Góra A, Rudzki S. Risk Factors for the Diagnosis of Colorectal Cancer. Cancer Control. 2022; 29:10732748211056692. https://doi. org/10.1177/10732748211056692.
Huang J, Pan H, Wang J, Wang T, Huo X, Ma Y, Lu Z, Sun B, Jiang H. Unfolded protein response in colorectal cancer. Cell Biosci. 2021;11(1):26.
Liang D, Khoonkari M, Avril T, Chevet E, Kruyt FAE. The unfolded protein response as regulator of cancer stemness and differentiation: Mechanisms and implications for cancer therapy. Biochem Pharmacol. 2021;192:114737.
Ritossa F. A new puffing pattern induced by temperature shock and DNP in drosophila. Experientia. 1962;18(12):571–573. https://doi. org/10.1007/BF02172188.
Laskey RA, Honda BM, Mills AD, Finch JT. Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA. Nature. 1978;275(5679):416–20.
Bailly C, Waring MJ. Pharmacological effectors of GRP78 chaperone in cancers. Biochem Pharmacol. 2019;163:269–278. https://doi. org/10.1016/j.bcp.2019.02.038.
Hendershot LM, Buck TM, Brodsky JL. The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis. J Mol Biol. BIPERA. 2023;168418.
Christianson JC, Carvalho P. Order through destruction: how ER- associated protein degradation contributes to organelle homeostasis. EMBO J. 2022;41(6):e109845.
Hetz C, Papa FR. The Unfolded Protein Response and Cell Fate Control. Mol Cell. 2018; 69(2):169–181. molcel.2017.06.017.
Perkins HT, Allan V. Intertwined and Finely Balanced: Endoplasmic Reticulum Morphology, Dynamics, Function, and Diseases. Cells. 2021;10(9):2341.
Marciniak SJ, Chambers JE, Ron D. Pharmacological targeting of endoplasmic reticulum stress in disease. Nat Rev Drug Discov 2022;21(2):115–140.
Abi Zamer B, El-Huneidi W, Eladl MA, Muhammad JS. Ins and Outs of Heat Shock Proteins in Colorectal Carcinoma: Its Role in Carcinogenesis and Therapeutic Perspectives. Cells. 2021;10(11):2862.
Shan Q, Ma F, Wei J, Li H, Ma H, Sun P. Physiological Functions of Heat Shock Proteins. Curr Protein Pept Sci. 2020;21(8):751–760. https://
Karagöz GE, Acosta-Alvear D, Walter P. The Unfolded Protein Response: Detecting and Responding to Fluctuations in the Protein-Folding Capacity of the Endoplasmic Reticulum. Cold Spring Harb Perspect Biol. 2019;11(9):a033886.
Krshnan L, van de Weijer ML, Carvalho P. Endoplasmic Reticulum- Associated Protein Degradation. Cold Spring Harb Perspect Biol. 2022;14(12):a041247.
Karagöz GE, Aragón T, Acosta-Alvear D. Recent advances in signal integration mechanisms in the unfolded protein response F1000Res. 2019;8:F1000 Faculty Rev-1840. f1000research.19848.1.
Adams CJ, Kopp MC, Larburu N, Nowak PR, Ali MMU. Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1. Front Mol Biosci. 2019;6:11. https://
Grey MJ, Cloots E, Simpson MS, LeDuc N, Serebrenik YV, De Luca H, De Sutter D, Luong P, Thiagarajah JR, Paton AW, Paton JC, Seeliger MA, Eyckerman S, Janssens S, Lencer WI. IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress. J Cell Biol. 2020;219(2):e201904048.
Shi W, Chen Z, Li L, Liu H, Zhang R, Cheng Q, Xu D, Wu L. Unravel the molecular mechanism of XBP1 in regulating the biology of cancer cells. J Cancer. 2019;10(9):2035–2046.
Liu S, Pi J, Zhang Q. Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway. Redox Biol. 2022;54:102389. https://
Siwecka N, Rozpędek-Kamińska W, Wawrzynkiewicz A, Pytel D, Diehl JA, Majsterek I. The Structure, Activation and Signaling of IRE1 and Its Role in Determining Cell Fate. Biomedicines. 2021;9(2):156. https://
Spaan NC, Wouter LS, Jooske FLJ, Meijer BJ, Muncan V, Van den Brink GR, Heijmans J. Expression of UPR effector proteins ATF6 and XBP1 reduce colorectal cancer cell proliferation and stemness by activating PERK signaling. Cell Death Dis. 2019;10(490). s41419-019-1729-4.
Alzahrani MR, Guan BJ, Zagore LL, Wu J, Chen CW, Licatalosi DD, Baker KE, Hatzoglou M. Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response. PLoS One. 2022;17(8):e0271695. https://
Márton M, Bánhegyi G, Gyöngyösi N, Kálmán EÉ, Pettkó-Szandtner A, Káldi K, Kapuy O. A systems biological analysis of the ATF4-GADD34- CHOP regulatory triangle upon endoplasmic reticulum stress. FEBS Open Bio. 2022;12(11):2065–2082. 5463.13484.
Hu H, Tian M, Ding C, Yu S. The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection. Front Immunol. 2019;9:3083.
Fu X, Cui J, Meng X, Jiang P, Zheng Q, Zhao W, Chen X.”Endoplasmic reticulum stress, cell death and tumour: Association between endoplasmic reticulum stress and the apoptosis pathway in tumours (Review)”. Oncology Reports. 2021;45(3):801–808.
Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative Stress in Cancer. Cancer Cell. 2020; 38(2):167–197. ccell.2020.06.001.
Schmitz ML, Shaban MS, Albert BV, Gökçen A, Kracht M. The Crosstalk of Endoplasmic Reticulum (ER) Stress Pathways with NF-κB: Complex Mechanisms Relevant for Cancer, Inflammation and Infection. Biomedicines. 2018;6(2):58. biomedicines6020058.
Liu K, Zhao C, Adajar RC, DeZwaan-McCabe D, Rutkowski DT. A beneficial adaptive role for CHOP in driving cell fate selection during ER stress. bioRxiv [Preprint]. 2023; 2023.03.19.533325. https://doi. org/10.1101/2023.03.19.533325.
Hsu SK, Chiu CC, Dahms HU, Chou CK, Cheng CM, Chang WT, Cheng KC, Wang HD, Lin IL. Unfolded Protein Response (UPR) in Survival, Dormancy, Immunosuppression, Metastasis, and Treatments of Cancer Cells. Int J Mol Sci. 2019;20(10):2518. ijms20102518.
Benedetti R, Gilardini Montani MS, Romeo MA, Arena A, Santarelli R, D’Orazi G, Cirone M. Role of UPR Sensor Activation in Cell Death-Survival Decision of Colon Cancer Cells Stressed by DPE Treatment. Biomedicines. 2021;9(9):1262. https://doi.org10.3390/ biomedicines9091262.
Read A, Schröder M. The Unfolded Protein Response: An Overview. Biology (Basel). 2021;10(5):384.
Siwecka N, Rozpędek W, Pytel D, Wawrzynkiewicz A, Dziki A, Dziki Ł, Diehl JA, Majsterek I. Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis. Int J Mol Sci. 2019;20(18):4354. ijms20184354.
Oakes SA. Endoplasmic Reticulum Stress Signaling in Cancer Cells. Am J Pathol. 2020;190(5):934–946. ajpath.2020.01.010.
Liu S, Gao Q, Li Y, Lun J, Yu M, Zhang H, Fang J. XBP1s acts as a transcription factor of IRE1α and promotes proliferation of colon cancer cells. Arch Biochem Biophys. 2023;737:109552. https://doi. org/10.1016/
Kiesel VA, Sheeley MP, Hicks EM, Andolino C, Donkin SS, Wendt MK, Hursting SD, Teegarden D. Hypoxia-Mediated ATF4 Induction Promotes Survival in Detached Conditions in Metastatic Murine Mammary Cancer Cells. Front Oncol. 2022;12:767479. https://doi. org/10.3389/fonc.2022.767479.
Hargadon KM. Tumour microenvironmental influences on dendritic cell and T cell function: A focus on clinically relevant immunologic and metabolic checkpoints. Clin Transl Med. 2020;10(1):374–411.
Khodakarami A, Adibfar S, Karpisheh V, Abolhasani S, Jalali P, Mohammadi H, Gholizadeh Navashenaq J, Hojjat-Farsangi M, Jadidi-Niaragh F. The molecular biology and therapeutic potential of Nrf2 in leukemia. Cancer Cell Int. 2022;22(1):241.
Iurlaro R, Muñoz-Pinedo C. Cell death induced by endoplasmic reticulum stress. FEBS J. 2016; 283(14):2640–52.
Lam M, Marsters SA, Ashkenazi A, Walter P. Misfolded proteins bind and activate death receptor 5 to trigger apoptosis during unresolved endoplasmic reticulum stress. Elife. 2020;9:e52291. https://doi. org/10.7554/eLife.52291.
Lin Y, Jiang M, Chen W, Zhao T, Wei Y. Cancer and ER stress: Mutual crosstalk between autophagy, oxidative stress and inflammatory response. Biomed Pharmacother. 2019;118:109249. https://doi. org/10.1016/j.biopha.2019.109249.
Macarulla T, Montagut C, Sánchez-Martin FJ, Granja M, Verdaguer H, Sastre J, Tabernero J. The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls. Expert Opin Biol Ther. 2020;20(1):15–22.
Izadpanah A, Willingham K, Chandrasekar B, Alt EU, Izadpanah R. Unfolded protein response and angiogenesis in malignancies. Biochim Biophys Acta Rev Cancer. 2023;1878(2):188839. https://doi. org/10.1016/j.bbcan.2022.188839.
Avril T, Vauléon E, Chevet E. Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers. Oncogenesis. 2017;6(8):e373.
Dauer P, Sharma NS, Gupta VK, Durden B, Hadad R, Banerjee S, Dudeja V, Saluja A, Banerjee S. ER stress sensor, glucose regulatory protein 78 (GRP78) regulates redox status in pancreatic cancer thereby maintaining “stemness”. Cell Death Dis. 2019;10(2):132. https://doi. org/10.1038/s41419-019-1408-5.
Hernandez I, Cohen M. Linking cell-surface GRP78 to cancer: From basic research to clinical value of GRP78 antibodies. Cancer Lett. 2022;524:1–14.
Akinyemi AO, Simpson KE, Oyelere SF, Nur M, Ngule CM, Owoyemi BCD, Ayarick VA, Oyelami FF, Obaleye O, Esoe DP, Liu X, Li Z. Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review. Mol Med. 2023;29(1):112.
Dong D, Stapleton C, Luo B, Xiong S, Ye W, Zhang Y, Jhaveri N, Zhu G, Ye R, Liu Z, Bruhn KW, Craft N, Groshen S, Hofman FM, Lee AS. A critical role for GRP78/BiP in the tumour microenvironment for neovascularization during tumour growth and metastasis. Cancer Res. 2011;71(8):2848–57.
Al-Keilani MS, Almomani BA, Alqudah MA, Alrjoub MM, Alzoubi HW, Shhabat BA. Immunohistochemical expression of GRP78 in relation to angiogenesis markers VEGF-a and CD31 and other histopathological parameters in NSCLC. Journal of Clinical Oncology. 2019;37(15).
Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumour necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem. 2001;276(17):13935–40.
Ji H, Huang C, Wu S, Kasim V. XBP1-s promotes colorectal cancer cell proliferation by inhibiting TAp73 transcriptional activity. Biochem Biophys Res Commun. 2019;508(1):203–209. bbrc.2018.11.112.
Chalmers F, Mogre S, Son J, Blazanin N, Glick AB. The multiple roles of the unfolded protein response regulator IRE1α in cancer. Mol Carcinog. 2019;58(9):1623–1630.
Kreß JKC, Jessen C, Hufnagel A, Schmitz W, Xavier da Silva TN, Ferreira Dos Santos A, Mosteo L, Goding CR, Friedmann Angeli JP, Meierjohann S. The integrated stress response effector ATF4 is an obligatory metabolic activator of NRF2. Cell Rep. 2023;42(7):112724.
Bhattarai KR, Riaz TA, Kim HR, Chae HJ. The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling. Exp Mol Med. 2021;53(2):151–167. s12276-021-00560-8.
Jiramongkol Y, Lam EW. FOXO transcription factor family in cancer and metastasis. Cancer Metastasis Rev. 2020;39(3):681–709. https://
Feng YX, Jin DX, Sokol ES, Reinhardt F, Miller DH, Gupta PB. Cancer- specific PERK signaling drives invasion and metastasis through CREB3L1. Nat Commun. 2017;8(1):1079. s41467-017-01052-y.
Qu J, Zou T, Lin Z. The Roles of the Ubiquitin-Proteasome System in the Endoplasmic Reticulum Stress Pathway. Int J Mol Sci. 2021;22(4):1526.
Coleman OI, Lobner EM, Bierwirth S, Sorbie A, Waldschmitt N, Rath E, Berger E, Lagkouvardos I, Clavel T, McCoy KD, Weber A, Heikenwalder M, Janssen KP, Haller D. Activated ATF6 Induces Intestinal Dysbiosis and Innate Immune Response to Promote Colorectal Tumourigenesis. Gastroenterology. 2018;155(5):1539–1552. e12.
Hanaoka M, Ishikawa T, Ishiguro M, Tokura M, Yamauchi S, Kikuchi A, Uetake H, Yasuno M, Kawano T. Expression of ATF6 as a marker of pre-cancerous atypical change in ulcerative colitis-associated colorectal cancer: a potential role in the management of dysplasia. J Gastroenterol. 2018;53(5):631–641.
Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, Zeevi D, Costea PI, Godneva A, Kalka IN, Bar N, Shilo S, Lador D, Vila AV, Zmora N, Pevsner-Fischer M, Israeli D, Kosower N, Malka G, Wolf BC, Avnit-Sagi T, Lotan-Pompan M, Weinberger A, Halpern Z, Carmi S, Fu J, Wijmenga C, Zhernakova A, Elinav E, Segal E. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555(7695):210–215.
Li J, Ma X, Chakravarti D, Shalapour S, DePinho RA. Genetic and biological hallmarks of colorectal cancer. Genes Dev. 2021;35(11–12):787–820.
Puzzono M, Mannucci A, Grannò S, Zuppardo RA, Galli A, Danese S, Cavestro GM. The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review. Cancers (Basel). 2021;13(23):5933.
Liang Q, Chiu J, Chen Y, Huang Y, Higashimori A, Fang J, Brim H, Ashktorab H, Ng SC, Ng SSM, Zheng S, Chan FKL, Sung JJY, Yu J. Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer. Clin Cancer Res. 2017;23(8):2061–2070. https://doi. org/10.1158/1078-0432.CCR-16-1599
Bourdeau-Julien I, Castonguay-Paradis S, Rochefort G, Perron J, Lamarche B, Flamand N, Di Marzo V, Veilleux A, Raymond F. The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population. Microbiome. 2023;11(1):26. https://
Chen Y, Chen YX. Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer. Cancers (Basel). 2021;13(16):4054. 68.
Yu I, Wu R, Tokumaru Y, Terracina KP, Takabe K. The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer. Cancers (Basel). 2022;14(22):5685.
Rubinstein MR, Baik JE, Lagana SM, Han RP, Raab WJ, Sahoo D, Dalerba P, Wang TC, Han YW. Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β-catenin modulator Annexin A1. EMBO Rep. 2019;20(4):e47638.
Lee CG, Hwang S, Gwon SY, Park C, Jo M, Hong JE, Rhee KJ. Bacteroides fragilis Toxin Induces Intestinal Epithelial Cell Secretion of Interleukin-8 by the E-Cadherin/β-Catenin/NF-κB Dependent Pathway. Biomedicines. 2022;10(4):827.
Chung L, Thiele Orberg E, Geis AL, Chan JL, Fu K, DeStefano Shields CE, Dejea CM, Fathi P, Chen J, Finard BB, Tam AJ, McAllister F, Fan H, Wu X, Ganguly S, Lebid A, Metz P, Van Meerbeke SW, Huso DL, Wick EC, Pardoll DM, Wan F, Wu S, Sears CL, Housseau F. Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host Microbe. 2018;23(2):203–214.e5.
Prizment AE, Staley C, Onyeaghala GC, Vivek S, Thyagarajan B, Straka RJ, Demmer RT, Knights D, Meyer KA, Shaukat A, Sadowsky MJ, Church TR. Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk. Aliment Pharmacol Ther. 2020;52(6):976– 987.
Kim C, Kim B. Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review. Nutrients. 2018;10(8):1021.
Rozpędek W, Pytel D, Wawrzynkiewicz A, Siwecka N, Dziki A, Dziki Ł, Diehl JA, Majsterek I. Use of Small-molecule Inhibitory Compound of PERK-dependent Signaling Pathway as a Promising Target-based Therapy for Colorectal Cancer. Curr Cancer Drug Targets. 2020;20(3):223–238. 6200106114826
Tsai HY, Ho CT, Chen YK. Biological actions and molecular effects of resveratrol, pterostilbene, and 3’-hydroxypterostilbene. J Food Drug Anal. 2017;25(1):134–147.
Wu R, Zhao J, Wei P, Tang M, Ma Z, Zhao Y, Du L, Wan L. Piper nigrum Extract Inhibits the Growth of Human Colorectal Cancer HT-29 Cells by Inducing p53-Mediated Apoptosis. Pharmaceuticals (Basel). 2023;16(9):1325.
Ismail NI, Othman I, Abas F, H Lajis N, Naidu R. Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer. Int J Mol Sci. 2019;20(10):2454.
Forsythe N, Refaat A, Javadi A, Khawaja H, Weir JA, Emam H, Allen WL, Burkamp F, Popovici V, Jithesh PV, Isella C, Labonte MJ, Mills IG, Johnston PG, Van Schaeybroeck S. The Unfolded Protein Response: A Novel Therapeutic Target for Poor Prognostic BRAF Mutant Colorectal Cancer. Mol Cancer Ther. 2018;17(6):1280–1290.
Gong C, Hu X, Xu Y, Yang J, Zong L, Wang C, Zhu J, Li Z, Lu D. Berberine inhibits proliferation and migration of colorectal cancer cells by downregulation of GRP78. Anticancer Drugs. 2020;31(2):141–149.
Li Z, Zhao C, Li Z, Zhao Y, Shan S, Shi T, Li J. Reconstructed mung bean trypsin inhibitor targeting cell surface GRP78 induces apoptosis and inhibits tumour growth in colorectal cancer. Int J Biochem Cell Biol. 2014;47:68–75. j.biocel.2013.11.022.
La X, Zhang L, Li Z, Li H, Yang Y. (-)-Epigallocatechin Gallate (EGCG) Enhances the Sensitivity of Colorectal Cancer Cells to 5-FU by Inhibiting GRP78/NF-κB/miR-155-5p/MDR1 Pathway. J Agric Food Chem. 2019;67(9):2510–2518.
Lv C, Qu H, Zhu W, Xu K, Xu A, Jia B, Qing Y, Li H, Wei HJ, Zhao HY. Low-Dose Paclitaxel Inhibits Tumour Cell Growth by Regulating Glutaminolysis in Colorectal Carcinoma Cells. Front Pharmacol. 2017;8:244.
Anselmino LE, Baglioni MV, Reynoso G, Rozados VR, Scharovsky OG, Rico MJ, Menacho-Márquez M. Potential effect of chloroquine and propranolol combination to treat colorectal and triple-negative breast cancers. Sci Rep. 2023;13(1):7923. 34793-6.
Gao Y, Wang J, Zhou Y, Sheng S, Qian SY, Huo X. Evaluation of Serum CEA, CA19-9, CA72-4, CA125 and Ferritin as Diagnostic Markers and Factors of Clinical Parameters for Colorectal Cancer. Sci Rep. 2018;8(1):2732.
Nassar FJ, Msheik ZS, Nasr RR, Temraz SN. Methylated circulating tumour DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction. Clin Epigenetics. 2021;13(1):111. https://
Malla M, Loree JM, Kasi PM, Parikh AR. Using Circulating Tumour DNA in Colorectal Cancer: Current and Evolving Practices. J Clin Oncol. 2022;40(24):2846–2857.
Benhaim L, Bouché O, Normand C, Didelot A, Mulot C, Le Corre D, Garrigou S, Djadi-Prat J, Wang-Renault SF, Perez-Toralla K, Pekin D, Poulet G, Landi B, Taieb J, Selvy M, Emile JF, Lecomte T, Blons H, Chatellier G, Link DR, Taly V, Laurent-Puig P. Circulating tumour DNA is a prognostic marker of tumour recurrence in stage II and III colorectal cancer: multicentric, prospective cohort study (ALGECOLS). Eur J Cancer. 2021;159:24–33.
Chen X, Li H, Guo F, Hoffmeister M, Brenner H. Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk. EClinicalMedicine. 2022;49:101460. eclinm.2022.101460.
Ferrari P, Jenab M, Norat T, Moskal A, Slimani N, Olsen A, Tjønneland A, Overvad K, Jensen MK, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Rohrmann S, Linseisen J, Boeing H, Bergmann M, Kontopoulou D, Trichopoulou A, Kassapa C, Masala G, Krogh V, Vineis P, Panico S, Tumino R, Gils CHV, Peeters P, Bueno-de-Mesquita HB, Ocké MC, Skeie G, Lund E, Agudo A, Ardanaz E, López DC, Sanchez MJ, Quirós JR, Amiano P, Berglund G, Manjer J, Palmqvist R, Guelpen BV, Allen N, Key T, Bingham S, Mazuir M, Boffetta P, Kaaks R, Riboli E. Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 2007;121(9):2065–2072. https://doi. org/10.1002/ijc.22966. PMID: 17640039.
McNabb S, Harrison TA, Albanes D, Berndt SI, Brenner H, Caan BJ, Campbell PT, Cao Y, Chang-Claude J, Chan A, Chen Z, English DR, Giles GG, Giovannucci EL, Goodman PJ, Hayes RB, Hoffmeister M, Jacobs EJ, Joshi AD, Larsson SC, Le Marchand L, Li L, Lin Y, Männistö S, Milne RL, Nan H, Newton CC, Ogino S, Parfrey PS, Petersen PS, Potter JD, Schoen RE, Slattery ML, Su YR, Tangen CM, Tucker TC, Weinstein SJ, White E, Wolk A, Woods MO, Phipps AI, Peters U. Meta-analysis of 16 studies of the association of alcohol with colorectal cancer. Int J Cancer. 2020;146(3):861–873. https://doi. org/10.1002/ijc.32377.
Cole BF, Logan RF, Halabi S, Benamouzig R, Sandler RS, Grainge MJ, Chaussade S, Baron JA. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst. 2009;101(4):256–66.
Grancher A, Michel P, Di Fiore F, Sefrioui D. Colorectal cancer chemoprevention: is aspirin still in the game? Cancer Biol Ther. 2022;23(1):446–461.
Elwood P, Morgan G, Watkins J, Protty M, Mason M, Adams R, Dolwani S, Pickering J, Delon C, Longley M. Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against. Br J Cancer. 2024;130(1):3–8. s41416-023-02506-5
Tomić T, Domínguez-López S, Barrios-Rodríguez R. Non-aspirin non- steroidal anti-inflammatory drugs in prevention of colorectal cancer in people aged 40 or older: A systematic review and meta-analysis. Cancer Epidemiol. 2019;58:52–62. https:/
Liu F, Yan L, Wang Z, Lu Y, Chu Y, Li X, Liu Y, Rui D, Nie S, Xiang H. Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis. Oncotarget. 2017;8(9):16017–16026. https://doi. org/10.18632/oncotarget.13762.
Hetz C, Zhang K, Kaufman RJ. Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol Cell Biol. 2020:421–438.
Zhang S, Guo S, Li Z, Li D, Zhan Q. High expression of hsp90 is associated with poor prognosis in patients with colorectal cancer. The Open Access Journal for Life & Enviroment Research. 2019 Oct;7:e7946. doi:10.7717/peerj.7946.
Basset CA, Conway de Macario E, Leone LG, Macario AJL, Leone A. The chaperone system in cancer therapies: hsp90. Journal of Molecular Histology. 2023 Mar;54:105–118. doi:10.1007/s10735-023-10119-8.
Brzozowa-Zasada M, Kurek J, Piecuch A, Wyrobiec G. The clinical and prognostic evaluation of grp94 immunoexpression in caucasian patients with colorectal adenocarcinoma. Przegląd Gastroenterologiczny. 2019 July;14(2):140-147. doi:10.5114/pg.2019.85898.
Kim JW, Cho YB, Lee S. Cell surface grp94 as a novel emerging therapeutic target for monoclonal antibody cancer therapy. Cells. 2021;10(5). doi:10.3390/cells10030670.
Bruno gG, Bergolis VL, Piscazzi A, Crispo F, Condelli V, Zoppoli P, Maddalena F, Pietrafesa M, Giordano G, Matassa DS, Esposito F, Landriscina M. Trap1 regulates the response of colorectal cancer cells to hypoxia and inhibits ribosome biogenesis under conditions of oxygen deprivation. International Journal of Oncology. 2022 Jun; 60(6). doi:10.3892/ijo.2022.5369.
Xie S, Wang X, Gan S, Tang X, Kang X, Zhu S. The mitochondrial chaperone trap1 as a candidate target of oncotherapy. Frontiers of Oncology. 2021 Jan;10:2020. doi:10.3389/fonc.2020.585047.
Jiang W, Pan X, Yan H, Wang G. Prognostic significance of the hsp70 gene family in colorectal cancer. Medical Science Monitor. 2021 Feb;27:e928352-1-e928352-13. doi:10.12659/msm.928352.
Zhao K, Zhou G, Liu Y, Zhang J, Chen Y, Liu L, Zhang G. Hsp70 family in cancer: signaling mechanisms and therapeutic advances. Biomolecules. 2023 Mar;13(4). doi:10.3390/biom13040601.
Feng YX, Sokol ES, del Vecchio CA, Sanduja S, Claessen JH, Proia TA, Jin DX, Reinhardt F, Ploegh HL, Wang Q, Gupta PB. Epithelial- to-mesenchymal transition activates perk-eif2α and sensitizes cells to endoplasmic reticulum stress. Cancer Discovery. 2014 Jun 4(6):702– 715. doi:10.1158/
Xi J, Chen Y, Huang S, Cui F, Wang X. Suppression of GRP78 sensitizes human colorectal cancer cells to oxaliplatin by downregulation of CD24. Oncology Letters. 2018 Jun;15(6):9861–9867. doi:10.3892/ ol.2018.8549.
Liu Z, Liu Y, Long Y, Liu B, Wang X. Role of hsp27 in the multidrug sensitivity and resistance of colon cancer cells. Oncology Letters. 2020 Mar;19(3):2021–2027. doi:10.3892/ol.2020.11255.
Huang CY, Wei PL, Chen WY, Chang WC, Chang YJ. Silencing heat shock protein 27 inhibits the progression and metastasis of colorectal cancer (crc) by maintaining the stability of stromal interaction molecule 1 (stim1) proteins. Cells. 2018 Dec;7(12). doi:10.3390/cells7120262.
Kalioraki MA, Artemaki PI, Sklirou AD, Kontos CK, Adamopoulos PG, Papadopoulos IN, Trougakos IP, Scorilas A. Heat shock protein beta 3 (hspb3) is an unfavorable molecular biomarker in colorectal adenocarcinoma. Molecular carcinogenesis. 2020 Jan;59(1):116–125. doi:10.1002/mc.23133.
Li Q, Wang Y, Lai Y, Xu P, Yang Z. Hspb5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through erk signaling. Plos One. 2017 Aug;12(8): e0182588. doi:10.1371/ journal.pone.0182588.
Guo J, Zhu S, Deng H, Xu R. Hsp60-knockdown suppresses proliferation in colorectal cancer cells via activating the adenine/ ampk/mtor signaling pathway. Oncology Letters. 2021 Aug;22(2). doi:10.3892/ol.2021.12891
Zeng J, Sanders A, Hargest R, Ye L, Jiang W. P-266 expression of hsp60 in colorectal cancer and implication in chemotherapeutic responses. Annals of Oncology. 2022 Jun;33(4). doi:10.1016/j.annonc.2022.04.356.
Causse SZ, Marcion G, Chanteloup G, Uyanik B, Boudesco C, Grigorash BB, Douhard R, Dias AMM, Dumetier B, Dondaine L, Gozzi GJ, Moussay E, Paggetti J, Mirjolet C, de Thonel A, Dubrez L, Demidov ON, Gobbo J, Garrido C. Hsp110 translocates to the nucleus upon genotoxic chemotherapy and promotes dna repair in colorectal cancer cells. Oncogene. 2019 Apr;38(15):2767–2777. doi:10.1038/s41388-018-0616-2.
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