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Review

Molecular and cellular pathways in colorectal cancer: apoptosis, autophagy and inflammation as key players

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Pages 1279-1290 | Received 24 Apr 2022, Accepted 08 Jun 2022, Published online: 22 Jun 2022

References

  • Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
  • Parkin DM. International variation. Oncogene. 2004;23(38):6329–6340.
  • Center MM, Jemal A, Smith RA, et al. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59(6):366–378.
  • Bishehsari F, Mahdavinia M, Vacca M, et al. Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention. World J Gastroenterol. 2014;20(20):6055–6072.
  • Isbister WH. Colorectal cancer below age 40 in the kingdom of Saudi Arabia. Aust N Z J Surg. 1992;62(6):468–472.
  • Veruttipong D, Soliman AS, Gilbert SF, et al. Age distribution, polyps and rectal cancer in the egyptian population-based cancer registry. World J Gastroenterol. 2012;18(30):3997–4003.
  • Ponz de Leon M, Di Gregorio C. Pathology of colorectal cancer. Dig Liver Dis. 2001;33(4):372–388.
  • Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(6):2073–2087.e3.
  • Fleming M, Ravula S, Tatishchev SF, et al. Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol. 2012;3(3):153–173.
  • Armaghany T, Wilson JD, Chu Q, et al. Genetic alterations in colorectal cancer. Gastrointest Cancer Res. 2012;5(1):19–27.
  • Gryfe R, Swallow C, Bapat B, et al. Molecular biology of colorectal cancer. Curr Probl Cancer. 1997;21(5):233–300.
  • Gullulu O, Hehlgans S, Rodel C, et al. Tumor suppressor protein p53 and inhibitor of apoptosis proteins in colorectal cancer-A promising signaling network for therapeutic interventions. Cancers (Basel). 2021;13(4):624.
  • Ma J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res. 1997;57:1098–1102.
  • Porter RJ, Arends MJ, Churchhouse AMD, et al. Inflammatory bowel disease-associated colorectal cancer: translational risks from mechanisms to medicines. J Crohns Colitis. 2021;15:2131–2141.
  • Semlali A, Almutairi MH, Alamri A, et al. Expression and polymorphism of TSLP/TSLP receptors as potential diagnostic markers of colorectal cancer progression. Genes (Basel). 2021;12(9):1386.
  • Burada F, Nicoli ER, Ciurea ME, et al. Autophagy in colorectal cancer: an important switch from physiology to pathology. World J Gastrointest Oncol. 2015;7(11):271–284.
  • Watson AJ. Apoptosis and colorectal cancer. Gut. 2004;53(11):1701–1709.
  • Ramesh P, Medema JP. BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy. Apoptosis. 2020;25(5-6):305–320.
  • Koornstra JJ, de Jong S, Hollema H, et al. Changes in apoptosis during the development of colorectal cancer: a systematic review of the literature. Crit Rev Oncol Hematol. 2003;45(1):37–53.
  • Keku TO, Amin A, Galanko J, et al. Apoptosis in normal rectal mucosa, baseline adenoma characteristics, and risk of future adenomas. Cancer Epidemiol Biomarkers Prev. 2008;17(2):306–310.
  • Rubio CA, Slezak P. The unique pathology of nonpolypoid colorectal neoplasia in IBD. Gastrointest Endosc Clin N Am. 2014;24(3):455–468.
  • Bonnington SN, Rutter MD. Surveillance of colonic polyps: are we getting it right? World J Gastroenterol. 2016;22(6):1925–1934.
  • Tanaka T. Colorectal carcinogenesis: review of human and experimental animal studies. J Carcinog. 2009;8:5.
  • Gunawardene AR, Corfe BM, Staton CA. Classification and functions of enteroendocrine cells of the lower gastrointestinal tract. Int J Exp Pathol. 2011;92(4):219–231.
  • Umar S. Intestinal stem cells. Curr Gastroenterol Rep. 2010;12(5):340–348.
  • Powell DW, Pinchuk IV, Saada JI, et al. Mesenchymal cells of the intestinal lamina propria. Annu Rev Physiol. 2011;73:213–237.
  • Hall JF. Management of malignant adenomas. Clin Colon Rectal Surg. 2015;28(4):215–219.
  • Abraha AM, Ketema EB. Apoptotic pathways as a therapeutic target for colorectal cancer treatment. World J Gastrointest Oncol. 2016;8(8):583–591.
  • Koliaraki V, Pallangyo CK, Greten FR, et al. Mesenchymal cells in colon cancer. Gastroenterology. 2017;152(5):964–979.
  • Ong ML, Schofield JB. Assessment of lymph node involvement in colorectal cancer. World J Gastrointest Surg. 2016;8(3):179–192.
  • Fodde R. The APC gene in colorectal cancer. Eur J Cancer. 2002;38(7):867–871.
  • Kwong LN, Dove WF. APC and its modifiers in Colon cancer. Adv Exp Med Biol. 2009;656:85–106.
  • Hankey W, Frankel WL, Groden J. Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting. Cancer Metastasis Rev. 2018;37(1):159–172.
  • Li XL, Zhou J, Chen ZR, et al. P53 mutations in colorectal cancer – molecular pathogenesis and pharmacological reactivation. World J Gastroenterol. 2015;21(1):84–93.
  • O'Reilly MA. Redox activation of p21Cip1/WAF1/Sdi1: a multifunctional regulator of cell survival and death. Antioxid Redox Signal. 2005;7(1-2):108–118.
  • Koutsodontis G, Tentes I, Papakosta P, et al. Sp1 plays a critical role in the transcriptional activation of the human cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene by the p53 tumor suppressor protein. J Biol Chem. 2001;276(31):29116–29125.
  • Liebl MC, Hofmann TG. The role of p53 signaling in colorectal cancer. Cancers (Basel). 2021;13(9):2125.
  • Rivlin N, Brosh R, Oren M, et al. Mutations in the p53 tumor suppressor gene: important milestones at the various steps of tumorigenesis. Genes Cancer. 2011;2(4):466–474.
  • Michel M, Kaps L, Maderer A, et al. The role of p53 dysfunction in colorectal cancer and its implication for therapy. Cancers (Basel). 2021;13(10):2296.
  • Sinicrope FA, Ruan SB, Cleary KR, et al. Bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 1995;55(2):237–241.
  • Bosari S, Moneghini L, Graziani D, et al. Bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. Hum Pathol. 1995;26(5):534–540.
  • Hawkins N, Lees J, Hargrave R, et al. Pathological and genetic correlates of apoptosis in the progression of colorectal neoplasia. Tumour Biol. 1997;18(3):146–156.
  • Stolfi C, Pallone F, Monteleone G. Molecular targets of TRAIL-sensitizing agents in colorectal cancer. Int J Mol Sci. 2012;13(7):7886–7901.
  • Dai X, Zhang J, Arfuso F, et al. Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy. Exp Biol Med (Maywood). 2015;240(6):760–773.
  • Mohr A, Buneker C, Gough RP, et al. MnSOD protects colorectal cancer cells from TRAIL-induced apoptosis by inhibition of smac/DIABLO release. Oncogene. 2008;27(6):763–774.
  • Flanagan L, Kehoe J, Fay J, et al. High levels of X-linked inhibitor-of-Apoptosis protein (XIAP) are indicative of radio chemotherapy resistance in rectal cancer. Radiat Oncol. 2015;10:131.
  • Zhang L, Yu J. Role of apoptosis in colon cancer biology, therapy, and prevention. Curr Colorectal Cancer Rep. 2013;9(4):331–340.
  • Zeestraten EC, Benard A, Reimers MS, et al. The prognostic value of the apoptosis pathway in colorectal cancer: a review of the literature on biomarkers identified by immunohistochemistry. Biomark Cancer. 2013;5:13–29.
  • Galligan L, Longley DB, McEwan M, et al. Chemotherapy and TRAIL-mediated colon cancer cell death: the roles of p53, TRAIL receptors, and c-FLIP. Mol Cancer Ther. 2005;4(12):2026–2036.
  • Kim BR, Park SH, Jeong YA, et al. RUNX3 enhances TRAIL-induced apoptosis by upregulating DR5 in colorectal cancer. Oncogene. 2019;38(20):3903–3918.
  • Chiriac AE, Wollina U, Azoicai D. Flare-up of rosacea due to face mask in healthcare workers during COVID-19. Maedica (Bucur). 2020;15(3):416–417.
  • Stidham RW, Higgins PDR. Colorectal cancer in inflammatory bowel disease. Clin Colon Rectal Surg. 2018;31(3):168–178.
  • Smith G, Carey FA, Beattie J, et al. Mutations in APC, kirsten-ras, and p53–alternative genetic pathways to colorectal cancer. Proc. Natl. Acad. Sci. U.S.A. 2002;99(14):9433–9438.
  • Nakayama M, Oshima M. Mutant p53 in colon cancer. J Mol Cell Biol. 2019;11(4):267–276.
  • Gessani S, Belardelli F. Immune dysfunctions and immunotherapy in colorectal cancer: the role of dendritic cells. Cancers (Basel). 2019;11:1491.
  • Sconocchia G, Eppenberger S, Spagnoli GC, et al. NK cells and T cells cooperate during the clinical course of colorectal cancer. Oncoimmunology. 2014;3(8):e952197.
  • Zhong X, Chen B, Yang Z. The role of Tumor-Associated macrophages in colorectal carcinoma progression. Cell Physiol Biochem. 2018;45(1):356–365.
  • Pernot S, Terme M, Voron T, et al. Colorectal cancer and immunity: what we know and perspectives. World J Gastroenterol. 2014;20(14):3738–3750.
  • Dhatchinamoorthy K, Colbert JD, Rock KL. Cancer immune evasion through loss of MHC class I antigen presentation. Front Immunol. 2021;12:636568.
  • Obakan-Yerlikaya P, Arisan ED, Coker-Gurkan A, et al. Calreticulin is a fine tuning molecule in epibrassinolide-induced apoptosis through activating endoplasmic reticulum stress in Colon cancer cells. Mol Carcinog. 2017;56(6):1603–1619.
  • Song D, Liu H, Wu J, et al. Insights into the role of ERp57 in cancer. J Cancer. 2021;12(8):2456–2464.
  • Xiao L, Cen D, Gan H, et al. Adoptive transfer of NKG2D CAR mRNA-Engineered natural killer cells in colorectal cancer patients. Mol Ther. 2019;27(6):1114–1125.
  • Meckawy GR, Mohamed AM, Zaki WK, et al. Natural killer NKG2A and NKG2D in patients with colorectal cancer. J. Gastrointest. Oncol. 2019;10(2):218–225.
  • Liu Q, Li A, Tian Y, et al. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev. 2016;31:61–71.
  • Bie Y, Ge W, Yang Z, et al. The crucial role of CXCL8 and its receptors in colorectal liver metastasis. Dis Markers. 2019;2019:8023460.
  • Cabrero-de Las Heras S, Martinez-Balibrea E. CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer. World J Gastroenterol. 2018;24(42):4738–4749.
  • Shi Y, Riese DJ, 2nd, Shen J. The role of the CXCL12/CXCR4/CXCR7 chemokine axis in cancer. Front Pharmacol. 2020;11:574667.
  • Yoshuantari N, Heriyanto DS, Hutajulu SH, et al. Clinicopathologic significance of CXCL12 and CXCR4 expressions in patients with colorectal cancer. Gastroenterol Res Pract. 2018;2018:9613185.
  • Rubie C, Oliveira V, Kempf K, et al. Involvement of chemokine receptor CCR6 in colorectal cancer metastasis. Tumour Biol. 2006;27(3):166–174.
  • Ghadjar P, Coupland SE, Na IK, et al. Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer. J Clin Oncol. 2006;24(12):1910–1916.
  • Frick VO, Rubie C, Keilholz U, et al. Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: an overview. World J Gastroenterol. 2016;22(2):833–841.
  • Singh UP, Singh NP, Murphy EA, et al. Chemokine and cytokine levels in inflammatory bowel disease patients. Cytokine. 2016;77:44–49.
  • Kawada K, Hosogi H, Sonoshita M, et al. Chemokine receptor CXCR3 promotes Colon cancer metastasis to lymph nodes. Oncogene. 2007;26(32):4679–4688.
  • Kistner L, Doll D, Holtorf A, et al. Interferon-inducible CXC-chemokines are crucial immune modulators and survival predictors in colorectal cancer. Oncotarget. 2017;8(52):89998–90012.
  • Lucas C, Barnich N, Nguyen HTT. Microbiota, inflammation and colorectal cancer. Int J Mol Sci. 2017;18:1310.
  • Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021;6(1):291.
  • Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240–273. Table of Contents.
  • Strickertsson JA, Desler C, Martin-Bertelsen T, et al. Enterococcus faecalis infection causes inflammation, intracellular oxphos-independent ROS production, and DNA damage in human gastric cancer cells. PLoS One. 2013;8(4):e63147.
  • Chen XW, Zhou SF. Inflammation, cytokines, the IL-17/IL-6/STAT3/NF-kappaB axis, and tumorigenesis. Drug Des Devel Ther. 2015;9:2941–2946.
  • Proenca MA, Biselli JM, Succi M, et al. Relationship between Fusobacterium nucleatum, inflammatory mediators and microRNAs in colorectal carcinogenesis. World J Gastroenterol. 2018;24(47):5351–5365.
  • Zhou Z, Chen J, Yao H, et al. Fusobacterium and colorectal cancer. Front Oncol. 2018;8:371.
  • Masucci MT, Minopoli M, Carriero MV. Tumor associated neutrophils. Their role in tumorigenesis, metastasis, prognosis and therapy. Front Oncol. 2019;9:1146.
  • Peddareddigari VG, Wang D, Dubois RN. The tumor microenvironment in colorectal carcinogenesis. Cancer Microenviron. 2010;3(1):149–166.
  • Thiele Orberg E, Fan H, Tam AJ, et al. The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis. Mucosal Immunol. 2017;10(2):421–433.
  • Abdulamir AS, Hafidh RR, Abu Bakar F. The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role. J Exp Clin Cancer Res. 2011;30:11.
  • Cheng J, Fan XM. Role of cyclooxygenase-2 in gastric cancer development and progression. World J Gastroenterol. 2013;19(42):7361–7368.
  • Buc E, Dubois D, Sauvanet P, et al. High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PLoS One. 2013;8(2):e56964.
  • Guo GF, Jiang WQ, Zhang B, et al. Autophagy-related proteins beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer. WJG. 2011;17(43):4779–4786.
  • Kang MR, Kim MS, Oh JE, et al. Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability. J Pathol. 2009;217(5):702–706.
  • Cianfanelli V, Fuoco C, Lorente M, et al. AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol. 2015;17(1):20–30.
  • Kim MS, Jeong EG, Ahn CH, et al. Frameshift mutation of UVRAG, an autophagy-related gene, in gastric carcinomas with microsatellite instability. Hum Pathol. 2008;39(7):1059–1063.
  • Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126(2):451–459.
  • Wu Y, Yao J, Xie J, et al. The role of autophagy in colitis-associated colorectal cancer. Signal Transduct Target Ther. 2018;3:31.
  • Wagatsuma K, Nakase H. Contradictory effects of NLRP3 inflammasome regulatory mechanisms in colitis. Int J Mol Sci. 2020;21:8145.
  • Isidro RA, Appleyard CB. Colonic macrophage polarization in homeostasis, inflammation, and cancer. Am J Physiol Gastrointest Liver Physiol. 2016;311(1):G59–73.
  • Conciatori F, Bazzichetto C, Falcone I, et al. Role of mTOR signaling in tumor microenvironment: an overview. Int J Mol Sci. 2018;19:2453.
  • Liu C, Wang J, Yang Y, et al. Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice. Biochem Pharmacol. 2018;155:366–379.
  • Strisciuglio C, Duijvestein M, Verhaar AP, et al. Impaired autophagy leads to abnormal dendritic cell-epithelial cell interactions. J Crohns Colitis. 2013;7(7):534–541.
  • Xuan Y, Zhao S, Xiao X, et al. Inhibition of chaperonemediated autophagy reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer. Mol Med Rep. 2021;23(5):360.
  • Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221(1):3–12.
  • Yin K, Lee J, Liu Z, et al. Mitophagy protein PINK1 suppresses Colon tumor growth by metabolic reprogramming via p53 activation and reducing acetyl-CoA production. Cell Death Differ. 2021;28(8):2421–2435.
  • Xie Q, Liu Y, Li X. The interaction mechanism between autophagy and apoptosis in Colon cancer. Transl Oncol. 2020;13(12):100871.
  • Petroni G, Bagni G, Iorio J, et al. Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K. Cell Death Dis. 2020;11(3):161.
  • Zhao Z, Xia G, Li N, et al. Autophagy inhibition promotes bevacizumab-induced apoptosis and proliferation inhibition in colorectal cancer cells. J Cancer. 2018;9(18):3407–3416.
  • Vernousfaderani EK, Akhtari N, Rezaei S, et al. Resveratrol and colorectal cancer: a molecular approach to clinical researches. Curr Top Med Chem. 2021;21(29):2634–2646.
  • O'Connell J, Bennett MW, Nally K, et al. Altered mechanisms of apoptosis in colon cancer: Fas resistance and counterattack in the tumor-immune conflict. Ann N Y Acad Sci. 2000;910:178–192. discussion 93–5.
  • Hu X, Sui X, Li L, et al. Protocadherin 17 acts as a tumour suppressor inducing tumour cell apoptosis and autophagy, and is frequently methylated in gastric and colorectal cancers. J Pathol. 2013;229(1):62–73.
  • Qureshi-Baig K, Kuhn D, Viry E, et al. Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway. Autophagy. 2020;16(8):1436–1452.
  • Hartwich A, Konturek SJ, Pierzchalski P, et al. Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer. Int J Colorectal Dis. 2001;16(4):202–210.
  • Tyciakova S, Valova V, Svitkova B, et al. Overexpression of TNFα induces senescence, autophagy and mitochondrial dysfunctions in melanoma cells. BMC Cancer. 2021;21(1):507.
  • Bozkurt E, Dussmann H, Salvucci M, et al. TRAIL signaling promotes entosis in colorectal cancer. J Cell Biol. 2021;220:e202010030.
  • Marmol I, Sanchez-de-Diego C, Pradilla Dieste A, et al. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. 2017;18:197.
  • Sun Z, Qiu Z, Ma B, et al. Encorafenib enhances TRAIL-induced apoptosis of colorectal cancer cells dependent on p53/PUMA signaling. Cytotechnology. 2021;73(1):63–70.
  • Marikar FM, Jin G, Sheng W, et al. Metallothionein 2A an interactive protein linking phosphorylated FADD to NF-κB pathway leads to colorectal cancer formation. Chin Clin Oncol. 2016;5(6):76.
  • Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–899.
  • Li J, Huang L, Zhao H, et al. The role of interleukins in colorectal cancer. Int J Biol Sci. 2020;16(13):2323–2339.
  • Yao M, Lam EC, Kelly CR, et al. Cyclooxygenase-2 selective inhibition with NS-398 suppresses proliferation and invasiveness and delays liver metastasis in colorectal cancer. Br J Cancer. 2004;90(3):712–719.
  • Markman JL, Shiao SL. Impact of the immune system and immunotherapy in colorectal cancer. J Gastrointest Oncol. 2015;6(2):208–223.

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