Talin1 knockdown prohibits the proliferation and migration of colorectal cancer cells via the EMT signaling pathway Retraction in /10.3892/ol.2021.12943

Ji,Ling; Jiang,Feizhao; Cui,Xianping; Qin,Chengkun

doi:10.3892/ol.2019.10902

Talin1 knockdown prohibits the proliferation and migration of colorectal cancer cells via the EMT signaling pathway

Retraction in: /10.3892/ol.2021.12943

Authors:
- Ling Ji
- Feizhao Jiang
- Xianping Cui
- Chengkun Qin
View Affiliations

Affiliations: Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: September 20, 2019 https://doi.org/10.3892/ol.2019.10902
Pages: 5408-5416
Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second highest cause of cancer‑associated death worldwide. Talin1 activates integrins, which mediate cell adhesion, proliferation, tumorigenesis and metastasis. The aim of the present study was to determine talin1 expression levels in colorectal cancer (CRC) and investigate the role of talin1 in CRC proliferation and invasion in vitro and in vivo. Talin1 protein expression levels were detected in human CRC and adjacent normal tissues by immunohistochemistry. Talin1 short hairpin RNA and control vectors were designed and stably transfected into HCT116 CRC cells. Cell proliferation was determined by MTT assay. Cell migratory and invasive capabilities were detected by wound‑healing and Matrigel invasion assays. The expression of proteins in the epithelial‑to‑mesenchymal transition signaling pathway was determined by western blotting and reverse transcription‑quantitative PCR. The effect of talin1 on tumor growth was explored in vivo using BALB/c nude mice. Immunohistochemical analysis of CRC and adjacent normal tissue revealed that talin1 expression was upregulated in CRC. Talin1 knockdown significantly reduced the proliferation, migration and invasive ability of HCT116 cells compared with the control. Protein levels of phosphorylated STAT3 and vimentin were significantly lower in talin1‑knockdown HCT116 cell lines compared with the control, whereas protein levels of E‑cadherin were increased. Interleukin‑6 mRNA levels were significantly increased in patients' blood samples compared with blood samples from healthy controls, as well as in CRC compared with adjacent normal tissue. In vivo experiments demonstrated that talin1 knockdown reduced CRC tumor growth and weight in nude mice. In conclusion, Talin1 knockdown may prevent the proliferation and migration of CRC cells by downregulating various factors involved in the epithelial‑to‑mesenchymal transition process, such as phosphorylated STAT3 and vimentin; therefore, talin1 may provide a novel therapeutic target for CRC.

View Figures

View References

1	Pattison AM, Merlino DJ, Blomain ES and Waldman SA: Guanylyl cyclase C signaling axis and colon cancer prevention. World J Gastroenterol. 22:8070–8077. 2016. View Article : Google Scholar : PubMed/NCBI
2	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
3	Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global patterns and trends in colorectal cancer incidence and mortality. Gut. 66:683–691. 2017. View Article : Google Scholar : PubMed/NCBI
4	Frampton M and Houlston RS: Modeling the prevention of colorectal cancer from the combined impact of host and behavioral risk factors. Genet Med. 19:314–321. 2017. View Article : Google Scholar : PubMed/NCBI
5	Das M, Ithychanda S, Qin J and Plow EF: Mechanisms of talin-dependent integrin signaling and crosstalk. Biochim Biophys Acta. 1838:579–588. 2014. View Article : Google Scholar : PubMed/NCBI
6	Calderwood DA and Ginsberg MH: Talin forges the links between integrins and actin. Nat Cell Biol. 5:694–697. 2003. View Article : Google Scholar : PubMed/NCBI
7	Hu X, Jing C, Xu X, Nakazawa N, Cornish VW, Margadant FM and Sheetz MP: Cooperative vinculin binding to talin mapped by time-resolved super resolution microscopy. Nano Lett. 16:4062–4068. 2016. View Article : Google Scholar : PubMed/NCBI
8	Giancotti FG and Ruoslahti E: Integrin signaling. Science. 285:1028–1032. 1999. View Article : Google Scholar : PubMed/NCBI
9	Klapholz B and Brown NH: Talin-the master of integrin adhesions. J Cell Sci. 130:2435–2446. 2017. View Article : Google Scholar : PubMed/NCBI
10	Becam IE, Tanentzapf G, Lepesant JA, Brown NH and Huynh JR: Integrin-independent repression of cadherin transcription by talin during axis formation in Drosophila. Nat Cell Biol. 7:510–516. 2005. View Article : Google Scholar : PubMed/NCBI
11	Zhang JL, Qian YB, Zhu LX and Xiong QR: Talin1, a valuable marker for diagnosis and prognostic assessment of human hepatocelluar carcinomas. Asian Pac J Cancer Prev. 12:3265–3269. 2011.PubMed/NCBI
12	Sakamoto S and Kyprianou N: Targeting anoikis resistance in prostate cancer metastasis. Mol Aspects Med. 31:205–214. 2010. View Article : Google Scholar : PubMed/NCBI
13	Lai MT, Hua CH, Tsai MH, Wan L, Lin YJ, Chen CM, Chiu IW, Chan C, Tsai FJ and Jinn-Chyuan Sheu J: Talin-1 overexpression defines high risk for aggressive oral squamous cell carcinoma and promotes cancer metastasis. J Pathol. 224:367–376. 2011. View Article : Google Scholar : PubMed/NCBI
14	Chen P, Zheng X, Zhou Y, Xu Y, Zhu L and Qian Y: Talin-1 interaction network promotes hepatocellular carcinoma progression. J Cell Sci. 8:13003–13014. 2017.
15	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
16	Huang C, Yang G, Jiang T, Zhu G, Li H and Qiu Z: The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro. Neoplasma. 58:396–405. 2011. View Article : Google Scholar : PubMed/NCBI
17	Chang KC, Wu MH, Jones D, Chen FF and Tseng YL: Activation of STAT3 in thymic epithelial tumours correlates with tumour type and clinical behaviour. J Pathol. 210:224–233. 2006. View Article : Google Scholar : PubMed/NCBI
18	Kusaba T, Nakayama T, Yamazumi K, Yakata Y, Yoshizaki A, Nagayasu T and Sekine I: Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors. J Clin Pathol. 58:833–838. 2005. View Article : Google Scholar : PubMed/NCBI
19	Grandis JR, Drenning S, Zeng Q, Watkins SC, Melhem MF, Endo S, Johnson DE, Huang L, He Y and Kim JD: Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci USA. 97:4227–4232. 2000. View Article : Google Scholar : PubMed/NCBI
20	Dhir R, Ni Z, Lou W, DeMiguel F, Grandis JR and Gao AC: Stat3 activation in prostatic carcinomas. Prostate. 51:241–246. 2002. View Article : Google Scholar : PubMed/NCBI
21	Scholz A, Heinze S, Detjen KM, Peters M, Welzel M, Hauff P, Schirner M, Wiedenmann B and Rosewicz S: Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology. 125:891–905. 2003. View Article : Google Scholar : PubMed/NCBI
22	Grivennikov SI, Greten FR and Karin M: Immunity, inflammation and cancer. Cell. 140:883–899. 2010. View Article : Google Scholar : PubMed/NCBI
23	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
24	Garbers C, Hermanns HM, Schaper F, Muller-Newen G, Grotzinger J, Rose-John S and Scheller J: Plasticity and cross-talk of interleukin 6-type cytokines. Cytokine Growth Factor Rev. 23:85–97. 2012. View Article : Google Scholar : PubMed/NCBI
25	Middleton K, Jones J, Lwin Z and Coward JI: Interleukin-6: An angiogenic target in solid tumours. Crit Rev Oncol Hematol. 89:129–139. 2014. View Article : Google Scholar : PubMed/NCBI
26	Xu Q, Briggs J, Park S, Niu G, Kortylewski M, Zhang S, Gritsko T, Turkson J, Kay H, Semenza G, et al: Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene. 24:5552–5560. 2005. View Article : Google Scholar : PubMed/NCBI
27	Jung JE, Lee HG, Cho IH, Chung DH, Yoon SH, Yang YM, Lee JW, Choi S, Park JW, Ye SK and Chung MH: STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. FASEB J. 19:1296–1298. 2005. View Article : Google Scholar : PubMed/NCBI
28	Paleri V, Mehanna H and Wight RG: TNM classification of malignant tumours 7th edition: What's new for head and neck? Clin Otolaryngol. 35:270–272. 2010. View Article : Google Scholar : PubMed/NCBI
29	Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI
30	Wu Z, Li X, Sunkara M, Spearman H, Morris AJ and Huang C: PIPKIγ regulates focal adhesion dynamics and colon cancer cell invasion. PLoS One. 6:e247752011. View Article : Google Scholar : PubMed/NCBI
31	Liu B, Pang B, Hou X, Fan H, Liang N, Zheng S, Feng B, Liu W, Guo H, Xu S and Pang Q: Expression of high-mobility group AT-hook protein 2 and its prognostic significance in malignant gliomas. Hum Pathol. 45:1752–1758. 2014. View Article : Google Scholar : PubMed/NCBI
32	Xu N, Chen HJ, Chen SH, Xue XY, Chen H, Zheng QS, Wei Y, Li XD, Huang JB, Cai H and Sun XL: Upregulation of Talin-1 expression associates with advanced pathological features and predicts lymph node metastases and biochemical recurrence of prostate cancer. Medicine. 95:e43262016. View Article : Google Scholar : PubMed/NCBI
33	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
34	Avalle L, Camporeale A, Camperi A and Poli V: STAT3 in cancer: A double edged sword. Cytokine. 98:42–50. 2017. View Article : Google Scholar : PubMed/NCBI
35	Hodge DR, Hurt EM and Farrar WL: The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer. 41:2502–2512. 2005. View Article : Google Scholar : PubMed/NCBI
36	Critchley DR: Biochemical and structural properties of the integrin-associated cytoskeletal protein talin. Annu Rev Biophys. 38:235–254. 2009. View Article : Google Scholar : PubMed/NCBI
37	Anthis NJ, Wegener KL, Ye F, Kim C, Goult BT, Lowe ED, Vakonakis I, Bate N, Critchley DR, Ginsberg MH and Campbell ID: The structure of an integrin/talin complex reveals the basis of inside-out signal transduction. EMBO J. 28:3623–3632. 2009. View Article : Google Scholar : PubMed/NCBI
38	Kang W, Kim SH, Cho HJ, Jin J, Lee J, Joo KM and Nam DH: Talin1 targeting potentiates anti-angiogenic therapy by attenuating invasion and stem-like features of glioblastoma multiforme. Oncotarget. 6:27239–27251. 2015. View Article : Google Scholar : PubMed/NCBI
39	Muto M, Mori M, Hiwasa T, Takiguchi M, Iwadate Y, Uzawa A, Uchida T, Masuda H, Sugimoto K and Kuwabara S: Novel serum autoantibodies against talin1 in multiple sclerosis: Possible pathogenetic roles of the antibodies. J Neuroimmunol. 284:30–36. 2015. View Article : Google Scholar : PubMed/NCBI
40	Singel SM, Cornelius C, Batten K, Fasciani G, Wright WE, Lum L and Shay JW: A targeted RNAi screen of the breast cancer genome identifies KIF14 and TLN1 as genes that modulate docetaxel chemosensitivity in triple-negative breast cancer. Clin Cancer Res. 19:2061–2070. 2013. View Article : Google Scholar : PubMed/NCBI
41	Sen S, Ng WP and Kumar S: Contributions of talin-1 to glioma cell-matrix tensional homeostasis. J R Soc Interface. 9:1311–1317. 2012. View Article : Google Scholar : PubMed/NCBI
42	Kanamori H, Kawakami T, Effendi K, Yamazaki K, Mori T, Ebinuma H, Masugi Y, Du W, Nagasaka K, Ogiwara A, et al: Identification by differential tissue proteome analysis of talin-1 as a novel molecular marker of progression of hepatocellular carcinoma. Oncology. 80:406–415. 2011. View Article : Google Scholar : PubMed/NCBI
43	Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 15:178–196. 2014. View Article : Google Scholar : PubMed/NCBI
44	Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI
45	Kang Y and Massague J: Epithelial-mesenchymal transitions: Twist in development and metastasis. Cell. 118:277–279. 2004. View Article : Google Scholar : PubMed/NCBI
46	Onder TT, Gupta PB, Mani SA, Yang J, Lander ES and Weinberg RA: Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 68:3645–3654. 2008. View Article : Google Scholar : PubMed/NCBI
47	Grivennikov SI and Karin M: Inflammatory cytokines in cancer: Tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis. 70 (Suppl 1):i104–i108. 2011. View Article : Google Scholar : PubMed/NCBI
48	Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C and Flavell RA: Inflammation-induced cancer: Crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 13:759–771. 2013. View Article : Google Scholar : PubMed/NCBI
49	Eldesoky A, Shouma A, Mosaad Y and Elhawary A: Clinical relevance of serum vascular endothelial growth factor and interleukin-6 in patients with colorectal cancer. Saudi J Gastroenterol. 17:170–173. 2011. View Article : Google Scholar : PubMed/NCBI