KRAS inhibitors may prevent colorectal cancer metachronous metastasis by suppressing TGF‑β mediated epithelial‑mesenchymal transition
- Authors:
- Yaoyu Guo
- Chuling Hu
- Kuntai Cai
- Guojie Long
- Du Cai
- Zhaoliang Yu
- Xinxin Huang
- Zerong Cai
- Peishan Hu
- Yufeng Chen
- Feng Gao
- Xiaojian Wu
-
Affiliations: Guangdong Institute of Gastroenterology, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China, Department of General Surgery (Department of Pancreatic Hepatobiliary Surgery), The Sixth Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China - Published online on: November 8, 2024 https://doi.org/10.3892/mmr.2024.13389
- Article Number: 24
-
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Siegel RL, Miller KD, Wagle NS and Jemal A: Cancer statistics, 2023. CA Cancer J Clin. 73:17–48. 2023. View Article : Google Scholar : PubMed/NCBI | |
Cohen R and Platell CF: Metachronous colorectal cancer metastasis: Who, what, when and what to do about it. J Surg Oncol. 129:71–77. 2024. View Article : Google Scholar : PubMed/NCBI | |
Hansdotter P, Scherman P, Nikberg M, Petersen SH, Holmberg E, Rizell M, Naredi P and Syk I; COLOFOL study group, : Treatment and survival of patients with metachronous colorectal lung metastases. J Surg Oncol. 127:806–814. 2023. View Article : Google Scholar : PubMed/NCBI | |
Reboux N, Jooste V, Goungounga J, Robaszkiewicz M, Nousbaum JB and Bouvier AM: Incidence and survival in synchronous and metachronous liver metastases from colorectal cancer. JAMA Netw Open. 5:e22366662022. View Article : Google Scholar : PubMed/NCBI | |
Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, et al: Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol. 11:761–808. 2020. View Article : Google Scholar : PubMed/NCBI | |
Pfannschmidt J, Dienemann H and Hoffmann H: Surgical resection of pulmonary metastases from colorectal cancer: A systematic review of published series. Ann Thorac Surg. 84:324–338. 2007. View Article : Google Scholar : PubMed/NCBI | |
Biller LH and Schrag D: Diagnosis and treatment of metastatic colorectal cancer: A review. JAMA. 325:669–685. 2021. View Article : Google Scholar : PubMed/NCBI | |
Boutin AT, Liao WT, Wang M, Hwang SS, Karpinets TV, Cheung H, Chu GC, Jiang S, Hu J, Chang K, et al: Oncogenic Kras drives invasion and maintains metastases in colorectal cancer. Genes Dev. 31:370–382. 2017. View Article : Google Scholar : PubMed/NCBI | |
Lemieux E, Cagnol S, Beaudry K, Carrier J and Rivard N: Oncogenic KRAS signalling promotes the Wnt/β-catenin pathway through LRP6 in colorectal cancer. Oncogene. 34:4914–4927. 2015. View Article : Google Scholar : PubMed/NCBI | |
Feng Q, Liang L, Ren L, Chen J, Wei Y, Chang W, Zhu D, Lin Q, Zheng P and Xu J: A specific KRAS codon 13 mutation is an independent predictor for colorectal cancer metachronous distant metastases. Am J Cancer Res. 5:674–688. 2015.PubMed/NCBI | |
Ilm K, Kemmner W, Osterland M, Burock S, Koch G, Herrmann P, Schlag PM and Stein U: High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients. Mol Cancer. 14:382015. View Article : Google Scholar : PubMed/NCBI | |
Hao M, Li H, Wang K, Liu Y, Liang X and Ding L: Predicting metachronous liver metastasis in patients with colorectal cancer: Development and assessment of a new nomogram. World J Surg Oncol. 20:802022. View Article : Google Scholar : PubMed/NCBI | |
Herzberg BO and Manji GA: KRAS: druggable at last. Oncologist. 28:283–286. 2023. View Article : Google Scholar : PubMed/NCBI | |
Abubaker J, Bavi P, Al-Haqawi W, Sultana M, Al-Harbi S, Al-Sanea N, Abduljabbar A, Ashari LH, Alhomoud S, Al-Dayel F, et al: Prognostic significance of alterations in KRAS isoforms KRAS-4A/4B and KRAS mutations in colorectal carcinoma. J Pathol. 219:435–445. 2009. View Article : Google Scholar : PubMed/NCBI | |
Nusrat M and Yaeger R: KRAS inhibition in metastatic colorectal cancer: An update. Curr Opin Pharmacol. 68:1023432023. View Article : Google Scholar : PubMed/NCBI | |
Kim D, Herdeis L, Rudolph D, Zhao Y, Böttcher J, Vides A, Ayala-Santos CI, Pourfarjam Y, Cuevas-Navarro A, Xue JY, et al: Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature. 619:160–166. 2023. View Article : Google Scholar : PubMed/NCBI | |
Ji Q, Liu X, Han Z, Zhou L, Sui H, Yan L, Jiang H, Ren J, Cai J and Li Q: Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression. BMC Cancer. 15:972015. View Article : Google Scholar : PubMed/NCBI | |
Moher D, Liberati A, Tetzlaff J and Altman DG; Group P, : Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 6:e10000972009. View Article : Google Scholar : PubMed/NCBI | |
Chatila WK, Kim JK, Walch H, Marco MR, Chen CT, Wu F, Omer DM, Khalil DN, Ganesh K, Qu X, et al: Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer. Nat Med. 28:1646–1655. 2022. View Article : Google Scholar : PubMed/NCBI | |
Roelands J, Kuppen PJK, Ahmed EI, Mall R, Masoodi T, Singh P, Monaco G, Raynaud C, de Miranda NFCC, Ferraro L, et al: An integrated tumor, immune and microbiome atlas of colon cancer. Nat Med. 29:1273–1286. 2023. View Article : Google Scholar : PubMed/NCBI | |
Medico E, Russo M, Picco G, Cancelliere C, Valtorta E, Corti G, Buscarino M, Isella C, Lamba S, Martinoglio B, et al: The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets. Nat Commun. 6:70022015. View Article : Google Scholar : PubMed/NCBI | |
Kim WK, Kwon Y, Jang M, Park M, Kim J, Cho S, Jang DG, Lee WB, Jung SH, Choi HJ, et al: β-catenin activation down-regulates cell-cell junction-related genes and induces epithelial-to-mesenchymal transition in colorectal cancers. Sci Rep. 9:184402019. View Article : Google Scholar : PubMed/NCBI | |
Yu Z, Deng P, Chen Y, Liu S, Chen J, Yang Z, Chen J, Fan X, Wang P, Cai Z, et al: Inhibition of the PLK1-coupled cell cycle machinery overcomes resistance to oxaliplatin in colorectal cancer. Adv Sci (Weinh). 8:e21007592021. View Article : Google Scholar : PubMed/NCBI | |
Chen S, Zhou Y, Chen Y and Gu J: fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 34:i884–i890. 2018. View Article : Google Scholar : PubMed/NCBI | |
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M and Gingeras TR: STAR: Ultrafast universal RNA-seq aligner. Bioinformatics. 29:15–21. 2013. View Article : Google Scholar : PubMed/NCBI | |
Li B and Dewey CN: RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 12:3232011. View Article : Google Scholar : PubMed/NCBI | |
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI | |
Kanehisa M, Furumichi M, Sato Y, Matsuura Y and Ishiguro-Watanabe M: KEGG: Biological systems database as a model of the real world. Nucleic Acids Res. gkae9092024.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI | |
Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP and Tamayo P: The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst. 1:417–425. 2015. View Article : Google Scholar : PubMed/NCBI | |
Engstrand J, Stromberg C, Nilsson H, Freedman J and Jonas E: Synchronous and metachronous liver metastases in patients with colorectal cancer-towards a clinically relevant definition. World J Surg Oncol. 17:2282019. View Article : Google Scholar : PubMed/NCBI | |
Kuan TC, Chang SC, Lin JK, Lin TC, Yang SH, Jiang JK, Chen WS, Wang HS, Lan YT, Lin CC, et al: Prognosticators of long-term outcomes of TNM stage II colorectal cancer: Molecular patterns or clinicopathological features. World J Surg. 43:3207–3215. 2019. View Article : Google Scholar : PubMed/NCBI | |
Jo P, Bernhardt M, Nietert M, König A, Azizian A, Schirmer MA, Grade M, Kitz J, Reuter-Jessen K, Ghadimi M, et al: KRAS mutation status concordance between the primary tumor and the corresponding metastasis in patients with rectal cancer. PLoS One. 15:e02398062020. View Article : Google Scholar : PubMed/NCBI | |
Lin CC, Lin JK, Lin TC, Chen WS, Yang SH, Wang HS, Lan YT, Jiang JK, Yang MH and Chang SC: The prognostic role of microsatellite instability, codon-specific KRAS, and BRAF mutations in colon cancer. J Surg Oncol. 110:451–457. 2014. View Article : Google Scholar : PubMed/NCBI | |
Tsunoda A, Iijima T, Tsunoda Y, Nakao K, Miyaki M and Kusano M: Association of K-ras mutations with liver metastases from colorectal carcinoma. Anticancer Res. 24:2471–2476. 2004.PubMed/NCBI | |
Vakiani E, Shah RH, Berger MF, Makohon-Moore AP, Reiter JG, Ostrovnaya I, Attiyeh MA, Cercek A, Shia J, Iacobuzio-Donahue CA, et al: Local recurrences at the anastomotic area are clonally related to the primary tumor in sporadic colorectal carcinoma. Oncotarget. 8:42487–42494. 2017. View Article : Google Scholar : PubMed/NCBI | |
Sperlich A, Balmert A, Doll D, Bauer S, Franke F, Keller G, Wilhelm D, Mur A, Respondek M, Friess H, et al: Genetic and immunological biomarkers predict metastatic disease recurrence in stage III colon cancer. BMC Cancer. 18:9982018. View Article : Google Scholar : PubMed/NCBI | |
Nitsche U, Rosenberg R, Balmert A, Schuster T, Slotta-Huspenina J, Herrmann P, Bader FG, Friess H, Schlag PM, Stein U and Janssen KP: Integrative marker analysis allows risk assessment for metastasis in stage II colon cancer. Ann Surg. 256:763–771. 2012. View Article : Google Scholar : PubMed/NCBI | |
Nakamura Y, Yokoyama S, Matsuda K, Tamura K, Mitani Y, Iwamoto H, Mizumoto Y, Murakami D, Kitahata Y and Yamaue H: Preoperative detection of KRAS mutated circulating tumor DNA is an independent risk factor for recurrence in colorectal cancer. Sci Rep. 11:4412021. View Article : Google Scholar : PubMed/NCBI | |
Huang SC, Huang SF, Chen YT, Chang Y, Chiu YT, Chang IC, Wu HI and Chen JS: Overexpression of MutL homolog 1 and MutS homolog 2 proteins have reversed prognostic implications for stage I–II colon cancer patients. Biomed J. 40:39–48. 2017. View Article : Google Scholar : PubMed/NCBI | |
El Otmani I, El Agy F, El Baradai S, Bouguenouch L, Lahmidani N, El Abkari M, Benajah DA, Toughrai I, El Bouhaddouti H, Mouaqit O, et al: Analysis of molecular pretreated tumor profiles as predictive biomarkers of therapeutic response and survival outcomes after neoadjuvant therapy for rectal cancer in moroccan population. Dis Markers. 2020:84593032020. View Article : Google Scholar : PubMed/NCBI | |
Birgisson H, Edlund K, Wallin U, Påhlman L, Kultima HG, Mayrhofer M, Micke P, Isaksson A, Botling J, Glimelius B and Sundström M: Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer. BMC Cancer. 15:1252015. View Article : Google Scholar : PubMed/NCBI | |
Verhagen MP, Xu T, Stabile R, Joosten R, Tucci FA, van Royen M, Trerotola M, Alberti S, Sacchetti A and Fodde R: The SW480 cell line as a model of resident and migrating colon cancer stem cells. iScience. 27:1106582024. View Article : Google Scholar : PubMed/NCBI | |
Dhillon S: Adagrasib: First approval. Drugs. 83:275–285. 2023. View Article : Google Scholar : PubMed/NCBI | |
Awad MM, Liu S, Rybkin II, Arbour KC, Dilly J, Zhu VW, Johnson ML, Heist RS, Patil T, Riely GJ, et al: Acquired resistance to KRASG12C inhibition in cancer. N Engl J Med. 384:2382–2393. 2021. View Article : Google Scholar : PubMed/NCBI | |
Flum M, Dicks S, Teng YH, Schrempp M, Nyström A, Boerries M and Hecht A: Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT. Oncogen. 41:1492–1506. 2022. View Article : Google Scholar | |
Sánchez-Tilló E, Pedrosa L, Vila I, Chen Y, Győrffy B, Sánchez-Moral L, Siles L, Lozano JJ, Esteve-Codina A, Darling DS, et al: The EMT factor ZEB1 paradoxically inhibits EMT in BRAF-mutant carcinomas. JCI Insight. 8:e1646292023. View Article : Google Scholar : PubMed/NCBI | |
Lee JK, Sivakumar S, Schrock AB, Madison R, Fabrizio D, Gjoerup O, Ross JS, Frampton GM, Napalkov P, Montesion M, et al: Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors. NPJ Precis Oncol. 6:912022. View Article : Google Scholar : PubMed/NCBI | |
Huang D, Sun W, Zhou Y, Li P, Chen F, Chen H, Xia D, Xu E, Lai M, Wu Y and Zhang H: Mutations of key driver genes in colorectal cancer progression and metastasis. Cancer Metastasis Rev. 37:173–187. 2018. View Article : Google Scholar : PubMed/NCBI | |
Meng M, Zhong K, Jiang T, Liu Z, Kwan HY and Su T: The current understanding on the impact of KRAS on colorectal cancer. Biomed Pharmacother. 140:1117172021. View Article : Google Scholar : PubMed/NCBI | |
Pereira AAL, Rego JFM, Morris V, Overman MJ, Eng C, Garrett CR, Boutin AT, Ferrarotto R, Lee M, Jiang ZQ, et al: Association between KRAS mutation and lung meta-stasis in advanced colorectal cancer. Br J Cancer. 112:424–428. 2015. View Article : Google Scholar : PubMed/NCBI | |
Tie J, Lipton L, Desai J, Gibbs P, Jorissen RN, Christie M, Drummond KJ, Thomson BN, Usatoff V, Evans PM, et al: KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clin Cancer Res. 17:1122–1130. 2011. View Article : Google Scholar : PubMed/NCBI | |
Guo L, Wang Y, Yang W, Wang C, Guo T, Yang J, Shao Z, Cai G, Cai S, Zhang L, et al: Molecular profiling provides clinical insights into targeted and immunotherapies as well as colorectal cancer prognosis. Gastroenterology. 165:414–428.e7. 2023. View Article : Google Scholar : PubMed/NCBI | |
Iseas S, Sendoya JM, Robbio J, Coraglio M, Kujaruk M, Mikolaitis V, Rizzolo M, Cabanne A, Ruiz G, Salanova R, et al: Prognostic impact of an integrative landscape of clinical, immune, and molecular features in non-metastatic rectal cancer. Front Oncol. 11:8018802022. View Article : Google Scholar : PubMed/NCBI | |
Misale S, Di Nicolantonio F, Sartore-Bianchi A, Siena S and Bardelli A: Resistance to anti-EGFR therapy in colorectal cancer: From heterogeneity to convergent evolution. Cancer Discov. 4:1269–1280. 2014. View Article : Google Scholar : PubMed/NCBI | |
Lal N, White BS, Goussous G, Pickles O, Mason MJ, Beggs AD, Taniere P, Willcox BE, Guinney J and Middleton GW: KRAS mutation and consensus molecular subtypes 2 and 3 are independently associated with reduced immune infiltration and reactivity in colorectal cancer. Clin Cancer Res. 24:224–233. 2018. View Article : Google Scholar : PubMed/NCBI | |
Caughey BA and Strickler JH: Targeting KRAS-mutated gastrointestinal malignancies with small-molecule inhibitors: A new generation of breakthrough therapies. Drugs. 84:27–44. 2024. View Article : Google Scholar : PubMed/NCBI | |
Erlanson DA and Webster KR: Targeting mutant KRAS. Curr Opin Chem Biol. 62:101–108. 2021. View Article : Google Scholar : PubMed/NCBI | |
Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, Sudhakar N, Bowcut V, Baer BR, Ballard JA, et al: The KRASG12C Inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discov. 10:54–71. 2020. View Article : Google Scholar : PubMed/NCBI | |
Popat S, Hubner R and Houlston RS: Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 23:609–618. 2005. View Article : Google Scholar : PubMed/NCBI | |
Storojeva I, Boulay JL, Heinimann K, Ballabeni P, Terracciano L, Laffer U, Mild G, Herrmann R and Rochlitz C: Prognostic and predictive relevance of microsatellite instability in colorectal cancer. Oncol Rep. 14:241–249. 2005.PubMed/NCBI | |
Berg KCG, Eide PW, Eilertsen IA, Johannessen B, Bruun J, Danielsen SA, Bjørnslett M, Meza-Zepeda LA, Eknæs M, Lind GE, et al: Multi-omics of 34 colorectal cancer cell lines-a resource for biomedical studies. Mol Cancer. 16:1162017. View Article : Google Scholar : PubMed/NCBI | |
Vu T and Datta P: Regulation of EMT in colorectal cancer: A culprit in metastasis. Cancers (Basel). 9:1712017. View Article : Google Scholar : PubMed/NCBI | |
Wang K, Song K, Ma Z, Yao Y, Liu C, Yang J, Xiao H, Zhang J, Zhang Y and Zhao W: Identification of EMT-related high-risk stage II colorectal cancer and characterisation of metastasis-related genes. Br J Cancer. 123:410–417. 2020. View Article : Google Scholar : PubMed/NCBI | |
Chu PC, Lin PC, Wu HY, Lin KT, Wu C, Bekaii-Saab T, Lin YJ, Lee CT, Lee JC and Chen CS: Mutant KRAS promotes liver metastasis of colorectal cancer, in part, by upregulating the MEK-Sp1-DNMT1-miR-137-YB-1-IGF-IR signaling pathway. Oncogene. 37:3440–3455. 2018. View Article : Google Scholar : PubMed/NCBI | |
Adachi Y, Kimura R, Hirade K, Yanase S, Nishioka Y, Kasuga N, Yamaguchi R and Ebi H: Scribble mis-localization induces adaptive resistance to KRAS G12C inhibitors through feedback activation of MAPK signaling mediated by YAP-induced MRAS. Nat Cancer. 4:829–843. 2023. View Article : Google Scholar : PubMed/NCBI | |
Vivekanandhan S and Mukhopadhyay D: Genetic status of KRAS influences transforming growth factor-beta (TGF-β) signaling: An insight into neuropilin-1 (NRP1) mediated tumorigenesis. Semin Cancer Biol. 54:72–79. 2019. View Article : Google Scholar : PubMed/NCBI | |
Pohl M, Radacz Y, Pawlik N, Schoeneck A, Baldus SE, Munding J, Schmiegel W, Schwarte-Waldhoff I and Reinacher-Schick A: SMAD4 mediates mesenchymal-epithelial reversion in SW480 colon carcinoma cells. Anticancer Res. 30:2603–2613. 2010.PubMed/NCBI | |
Lee J, Ballikaya S, Schönig K, Ball CR, Glimm H, Kopitz J and Gebert J: Transforming growth factor beta receptor 2 (TGFBR2) changes sialylation in the microsatellite unstable (MSI) Colorectal cancer cell line HCT116. PLoS One. 8:e570742013. View Article : Google Scholar : PubMed/NCBI | |
Hawinkels LJAC, Paauwe M, Verspaget HW, Wiercinska E, van der Zon JM, van der Ploeg K, Koelink PJ, Lindeman JH, Mesker W, ten Dijke P and Sier CF: Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts. Oncogene. 33:97–107. 2014. View Article : Google Scholar : PubMed/NCBI |