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KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells

  • Authors:
    • Madhura Patankar
    • Sinikka Eskelinen
    • Anne Tuomisto
    • Markus J. Mäkinen
    • Tuomo J. Karttunen
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    Affiliations: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
    Copyright: © Patankar et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Pages: 4634-4644
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    Published online on: September 20, 2019
       https://doi.org/10.3892/mmr.2019.10693
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Abstract

In a number of types of cancer, anoikis, a form of apoptosis induced by loss of extracellular matrix (ECM) attachment, is disturbed. Anoikis resistance is essential in the formation of metastases. A recent study identified carcinoma cell subpopulations surviving without ECM contact in pathological specimens of colorectal cancer. The occurrence of these subpopulations indicated anoikis resistance. In the present study, it is demonstrated that KRAS and BRAF mutations induce anoikis resistance in colon cancer (Caco‑2) cells. In 3D cultures, Caco‑2 cells transfected with mutated KRAS or BRAF formed multicellular structures analogous to anoikis‑resistant subpopulations in actual carcinomas, and serve as an in vitro model for anoikis resistance. Caco‑2 cell lines were constructed, with KRAS or BRAF mutations, using retroviral delivery. The current study investigated anoikis resistance using an Annexin V apoptosis test from suspension cultures. 3D in vitro cultures, which were generated in collagen‑matrigel mixtures, were assessed using confocal microscopy. 3D cultures embedded in paraffin were analyzed using conventional histopathology. In suspension cultures, Caco‑2 cells with KRAS or BRAF mutations indicated a significantly lower proportion of Annexin positivity than the native Caco‑2 cells, indicating that these mutations induce anoikis resistance in Caco‑2 cells. 3D cultures displayed native Caco‑2 cells forming polarized cysts with a single layer thick epithelium, whereas Caco‑2 cells with KRAS or BRAF mutations formed partially filled cystic structures or solid round structures where only the outermost layer was in contact with the ECM. Additionally, KRAS mutations induced reversed polarity to Caco‑2 cells along with the emergence of solid growth. The present study demonstrated that KRAS and BRAF mutations induce anoikis resistance in Caco‑2 colorectal cancer cells. The growth patterns generated from the KRAS and BRAF mutated cells in 3D cultures revealed a resemblance to the putative anoikis‑resistant subpopulations in actual carcinomas, including micropapillary structures and solid tumor cell islands. Additionally, KRAS mutation induced the emergence of inverted polarity. In conclusion, 3D cultures with modified Caco‑2 cells serve as a valid in vitro model for anoikis resistance and inverted polarity.
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1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Arrington AK, Heinrich EL, Lee W, Duldulao M, Patel S, Sanchez J, Garcia-Aguilar J and Kim J: Prognostic and predictive roles of KRAS mutation in colorectal cancer. Int J Mol Sci. 13:12153–12168. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Stefanius K, Ylitalo L, Tuomisto A, Kuivila R, Kantola T, Sirnio P, Karttunen TJ and Mäkinen MJ: Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma. Histopathology. 58:679–692. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Neumann J, Zeindl-Eberhart E, Kirchner T and Jung A: Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract. 205:858–862. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Foltran L, De Maglio G, Pella N, Ermacora P, Aprile G, Masiero E, Giovannoni M, Iaiza E, Cardellino GG, Lutrino SE, et al: Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer. Future Oncol. 11:629–640. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Guo F, Gong H, Zhao H, Chen J, Zhang Y, Zhang L, Shi X, Zhang A, Jin H, Zhang J and He Y: Mutation status and prognostic values of KRAS, NRAS, BRAF and PIK3CA in 353 chinese colorectal cancer patients. Sci Rep. 8:60762018. View Article : Google Scholar : PubMed/NCBI

7 

Matallanas D, Birtwistle M, Romano D, Zebisch A, Rauch J, von Kriegsheim A and Kolch W: Raf family kinases: Old dogs have learned new tricks. Genes Cancer. 2:232–260. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Yokota T, Ura T, Shibata N, Takahari D, Shitara K, Nomura M, Kondo C, Mizota A, Utsunomiya S, Muro K and Yatabe Y: BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer. 104:856–862. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Lai E, Pretta A, Impera V, Mariani S, Giampieri R, Casula L, Pusceddu V, Coni P, Fanni D, Puzzoni M, et al: BRAF-mutant colorectal cancer, a different breed evolving. Expert Rev Mol Diagn. 18:499–512. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Gilmore AP: Anoikis. Cell Death Differ. 12 (Suppl 2):S1473–S1477. 2005. View Article : Google Scholar

11 

Guadamillas MC, Cerezo A and Del Pozo MA: Overcoming anoikis-pathways to anchorage-independent growth in cancer. J Cell Sci. 124:3189–3197. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Jinka R, Kapoor R, Sistla PG, Raj TA and Pande G: Alterations in cell-extracellular matrix interactions during progression of cancers. Int J Cell Biol. 2012:2191962012. View Article : Google Scholar : PubMed/NCBI

13 

Frisch SM and Ruoslahti E: Integrins and anoikis. Curr Opin Cell Biol. 9:701–706. 1997. View Article : Google Scholar : PubMed/NCBI

14 

Paoli P, Giannoni E and Chiarugi P: Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta. 1833:3481–3498. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Demers MJ, Thibodeau S, Noël D, Fujita N, Tsuruo T, Gauthier R, Arguin M and Vachon PH: Intestinal epithelial cancer cell anoikis resistance: EGFR-mediated sustained activation of Src overrides Fak-dependent signaling to MEK/Erk and/or PI3-K/Akt-1. J Cell Biochem. 107:639–654. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Mason JA, Davison-Versagli CA, Leliaert AK, Pape DJ, McCallister C, Zuo J, Durbin SM, Buchheit CL, Zhang S and Schafer ZT: Oncogenic Ras differentially regulates metabolism and anoikis in extracellular matrix-detached cells. Cell Death Differ. 23:1271–1282. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Guerrero S, Casanova I, Farré L, Mazo A, Capellà G and Mangues R: K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression. Cancer Res. 60:6750–6756. 2000.PubMed/NCBI

18 

Jones RP, Sutton PA, Evans JP, Clifford R, McAvoy A, Lewis J, Rousseau A, Mountford R, McWhirter D and Malik HZ: Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. Br J Cancer. 116:923–929. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Boisvert-Adamo K and Aplin AE: Mutant B-RAF mediates resistance to anoikis via bad and Bim. Oncogene. 27:3301–3312. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Goldstein NB, Johannes WU, Gadeliya AV, Green MR, Fujita M, Norris DA and Shellman YG: Active N-Ras and B-Raf inhibit anoikis by downregulating Bim expression in melanocytic cells. J Invest Dermatol. 129:432–437. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Kawakami H, Huang S, Pal K, Dutta SK, Mukhopadhyay D and Sinicrope FA: Mutant BRAF upregulates MCL-1 to confer apoptosis resistance that is reversed by MCL-1 antagonism and cobimetinib in colorectal cancer. Mol Cancer Ther. 15:3015–3027. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Patankar M, Vayrynen S, Tuomisto A, Makinen M, Eskelinen S and Karttunen TJ: Micropapillary structures in colorectal cancer: An anoikis-resistant subpopulation. Anticancer Res. 38:2915–2921. 2018.PubMed/NCBI

23 

Jia J, Zhang W, Liu JY, Chen G, Liu H, Zhong HY, Liu B, Cai Y, Zhang JL and Zhao YF: Epithelial mesenchymal transition is required for acquisition of anoikis resistance and metastatic potential in adenoid cystic carcinoma. PLoS One. 7:e515492012. View Article : Google Scholar : PubMed/NCBI

24 

Fofaria NM and Srivastava SK: STAT3 induces anoikis resistance, promotes cell invasion and metastatic potential in pancreatic cancer cells. Carcinogenesis. 36:142–150. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Cai Q, Yan L and Xu Y: Anoikis resistance is a critical feature of highly aggressive ovarian cancer cells. Oncogene. 34:3315–3324. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Herrmann D, Conway JR, Vennin C, Magenau A, Hughes WE, Morton JP and Timpson P: Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment. Carcinogenesis. 35:1671–1679. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Edmondson R, Broglie JJ, Adcock AF and Yang L: Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol. 12:207–218. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Weiswald LB, Bellet D and Dangles-Marie V: Spherical cancer models in tumor biology. Neoplasia. 17:1–15. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Fang Y and Eglen RM: Three-dimensional cell cultures in drug discovery and development. SLAS Discov. 22:456–472. 2017.PubMed/NCBI

30 

Langhans SA: Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front Pharmacol. 9:62018. View Article : Google Scholar : PubMed/NCBI

31 

Makrodouli E, Oikonomou E, Koc M, Andera L, Sasazuki T, Shirasawa S and Pintzas A: BRAF and RAS oncogenes regulate rho GTPase pathways to mediate migration and invasion properties in human colon cancer cells: A comparative study. Mol Cancer. 10:1182011. View Article : Google Scholar : PubMed/NCBI

32 

Magudia K, Lahoz A and Hall A: K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc. J Cell Biol. 198:185–194. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Debnath J, Muthuswamy SK and Brugge JS: Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods. 30:256–268. 2003. View Article : Google Scholar : PubMed/NCBI

34 

Camplejohn RS: Flow cytometric measurement of cell proliferation. Methods Mol Med. 57:133–143. 2001.PubMed/NCBI

35 

Pinto MP, Jacobsen BM and Horwitz KB: An immunohistochemical method to study breast cancer cell subpopulations and their growth regulation by hormones in three-dimensional cultures. Front Endocrinol (Lausanne). 2:152011. View Article : Google Scholar : PubMed/NCBI

36 

Kozlova NI, Morozevich GE, Chubukina AN and Berman AE: Integrin alphavbeta3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells. Oncogene. 20:4710–4717. 2001. View Article : Google Scholar : PubMed/NCBI

37 

Cremolini C, Di Maio M, Petrelli F, Berenato R, Loupakis F and Pietrantonio F: BRAF-mutated metastatic colorectal cancer between past and future. Br J Cancer. 113:1634–1635. 2015. View Article : Google Scholar : PubMed/NCBI

38 

Orlandi A, Calegari A, Inno A, Berenato R, Caporale M, Niger M, Bossi I, Di Bartolomeo M, de Braud F and Pietrantonio F: BRAF in metastatic colorectal cancer: The future starts now. Pharmacogenomics. 16:2069–2081. 2015. View Article : Google Scholar : PubMed/NCBI

39 

Pollan SG, Huang F, Sperger JM, Lang JM, Morrissey C, Cress AE, Chu CY, Bhowmick NA, You S, Freeman MR, et al: Regulation of inside-out β1-integrin activation by CDCP1. Oncogene. 37:2817–2836. 2018. View Article : Google Scholar : PubMed/NCBI

40 

Zhang X, Cromwell JW, Kunjummen BD, Yee D and Garcia-Aguilar J: The alpha2 and alpha3 integrins are required for morphologic differentiation of an intestinal epithelial cell line. Surgery. 133:429–437. 2003. View Article : Google Scholar : PubMed/NCBI

41 

Zajac O, Raingeaud J, Libanje F, Lefebvre C, Sabino D, Martins I, Roy P, Benatar C, Canet-Jourdan C, Azorin P, et al: Tumour spheres with inverted polarity drive the formation of peritoneal metastases in patients with hypermethylated colorectal carcinomas. Nat Cell Biol. 20:296–306. 2018. View Article : Google Scholar : PubMed/NCBI

42 

Clarke CN and Kopetz ES: BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: Clinical characteristics, clinical behavior, and response to targeted therapies. J Gastrointest Oncol. 6:660–617. 2015.PubMed/NCBI

43 

Jang MH, Kim S, Hwang DY, Kim WY, Lim SD, Kim WS, Hwang TS and Han HS: BRAF-mutated colorectal cancer exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability status. J Korean Med Sci. 32:38–46. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Li Y and Li W: BRAF mutation is associated with poor clinicopathological outcomes in colorectal cancer: A meta-analysis. Saudi J Gastroenterol. 23:144–149. 2017.PubMed/NCBI

45 

Modest DP, Ricard I, Heinemann V, Hegewisch-Becker S, Schmiegel W, Porschen R, Stintzing S, Graeven U, Arnold D, von Weikersthal LF, et al: Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: Pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. Ann Oncol. 27:1746–1753. 2016. View Article : Google Scholar : PubMed/NCBI

46 

Fu T, Guzzetta AA, Jeschke J, Vatapalli R, Dave P, Hooker CM, Morgan R, Iacobuzio-Donahue CA, Liu B and Ahuja N: KRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma. Int J Cancer. 132:2502–2509. 2013. View Article : Google Scholar : PubMed/NCBI

47 

Margonis GA, Kim Y, Spolverato G, Ejaz A, Gupta R, Cosgrove D, Anders R, Karagkounis G, Choti MA and Pawlik TM: Association between specific mutations in KRAS codon 12 and colorectal liver metastasis. JAMA Surg. 150:722–179. 2015. View Article : Google Scholar : PubMed/NCBI

48 

Wickenden JA, Jin H, Johnson M, Gillings AS, Newson C, Austin M, Chell SD, Balmanno K, Pritchard CA and Cook SJ: Colorectal cancer cells with the BRAF(V600E) mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM. Oncogene. 27:7150–7161. 2008. View Article : Google Scholar : PubMed/NCBI

49 

Gogada R, Yadav N, Liu J, Tang S, Zhang D, Schneider A, Seshadri A, Sun L, Aldaz CM, Tang DG and Chandra D: Bim, a proapoptotic protein, up-regulated via transcription factor E2F1-dependent mechanism, functions as a prosurvival molecule in cancer. J Biol Chem. 288:368–381. 2013. View Article : Google Scholar : PubMed/NCBI

50 

Teräväinen TP, Myllymäki SM, Friedrichs J, Strohmeyer N, Moyano JV, Wu C, Matlin KS, Muller DJ and Manninen A: αV-integrins are required for mechanotransduction in MDCK epithelial cells. PLoS One. 8:e714852013. View Article : Google Scholar : PubMed/NCBI

51 

Ferreira LP, Gaspar VM and Mano JF: Design of spherically structured 3D in vitro tumor models-advances and prospects. Acta Biomater. 75:11–34. 2018. View Article : Google Scholar : PubMed/NCBI

52 

Stevens PD, Wen YA, Xiong X, Zaytseva YY, Li AT, Wang C, Stevens AT, Farmer TN, Gan T, Weiss HL, et al: Erbin suppresses KSR1-mediated RAS/RAF signaling and tumorigenesis in colorectal cancer. Cancer Res. 78:4839–4852. 2018. View Article : Google Scholar : PubMed/NCBI

53 

Riedl A, Schlederer M, Pudelko K, Stadler M, Walter S, Unterleuthner D, Unger C, Kramer N, Hengstschlager M, Kenner L, et al: Comparison of cancer cells in 2D vs 3D culture reveals differences in AKT-mTOR-S6K signaling and drug responses. J Cell Sci. 130:203–218. 2017. View Article : Google Scholar : PubMed/NCBI

54 

Luca AC, Mersch S, Deenen R, Schmidt S, Messner I, Schäfer KL, Baldus SE, Huckenbeck W, Piekorz RP, Knoefel WT, et al: Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PLoS One. 8:e596892013. View Article : Google Scholar : PubMed/NCBI

55 

Derouet M, Wu X, May L, Hoon Yoo B, Sasazuki T, Shirasawa S, Rak J and Rosen KV: Acquisition of anoikis resistance promotes the emergence of oncogenic K-ras mutations in colorectal cancer cells and stimulates their tumorigenicity in vivo. Neoplasia. 9:536–545. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Patankar M, Eskelinen S, Tuomisto A, Mäkinen MJ and Karttunen TJ: KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells. Mol Med Rep 20: 4634-4644, 2019.
APA
Patankar, M., Eskelinen, S., Tuomisto, A., Mäkinen, M.J., & Karttunen, T.J. (2019). KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells. Molecular Medicine Reports, 20, 4634-4644. https://doi.org/10.3892/mmr.2019.10693
MLA
Patankar, M., Eskelinen, S., Tuomisto, A., Mäkinen, M. J., Karttunen, T. J."KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells". Molecular Medicine Reports 20.5 (2019): 4634-4644.
Chicago
Patankar, M., Eskelinen, S., Tuomisto, A., Mäkinen, M. J., Karttunen, T. J."KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells". Molecular Medicine Reports 20, no. 5 (2019): 4634-4644. https://doi.org/10.3892/mmr.2019.10693
Copy and paste a formatted citation
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Spandidos Publications style
Patankar M, Eskelinen S, Tuomisto A, Mäkinen MJ and Karttunen TJ: KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells. Mol Med Rep 20: 4634-4644, 2019.
APA
Patankar, M., Eskelinen, S., Tuomisto, A., Mäkinen, M.J., & Karttunen, T.J. (2019). KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells. Molecular Medicine Reports, 20, 4634-4644. https://doi.org/10.3892/mmr.2019.10693
MLA
Patankar, M., Eskelinen, S., Tuomisto, A., Mäkinen, M. J., Karttunen, T. J."KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells". Molecular Medicine Reports 20.5 (2019): 4634-4644.
Chicago
Patankar, M., Eskelinen, S., Tuomisto, A., Mäkinen, M. J., Karttunen, T. J."KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells". Molecular Medicine Reports 20, no. 5 (2019): 4634-4644. https://doi.org/10.3892/mmr.2019.10693
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