Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309–16.

PubMed  Google Scholar 

McCord C, Kiss A, Magalhaes MA, et al. Oral squamous cell carcinoma associated with precursor lesions. Cancer Prev Res. 2021;14:873–84.

Google Scholar 

Lin HJ, Wang XL, Tian MY, Li XL, Tan HZ. Betel quid chewing and oral potential malignant disorders and the impact of smoking and drinking: a meta-analysis. World J Clin Cases. 2022;10:3131–42.

PubMed  PubMed Central  Google Scholar 

Wen CP, Tsai SP, Cheng TY, et al. Uncovering the relation between betel quid chewing and cigarette smoking in Taiwan. Tob Control. 2005;14(1):i16-22.

PubMed  PubMed Central  Google Scholar 

Lee CH, Ko YC, Huang HL, et al. The precancer risk of betel quid chewing, tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan. Br J Cancer. 2003;88:366–72.

CAS  PubMed  PubMed Central  Google Scholar 

Wang B, Guo H, Yu H, et al. The role of the transcription factor EGR1 in cancer. Front Oncol. 2021;11: 642547.

CAS  PubMed  PubMed Central  Google Scholar 

Bhattacharyya S, Chen SJ, Wu M, et al. Smad-independent transforming growth factor-beta regulation of early growth response-1 and sustained expression in fibrosis: implications for scleroderma. Am J Pathol. 2008;173:1085–99.

CAS  PubMed  PubMed Central  Google Scholar 

Chen SJ, Ning H, Ishida W, et al. The early-immediate gene EGR-1 is induced by transforming growth factor-beta and mediates stimulation of collagen gene expression. J Biol Chem. 2006;281:21183–97.

CAS  PubMed  Google Scholar 

Yasuoka H, Hsu E, Ruiz XD, et al. The fibrotic phenotype induced by IGFBP-5 is regulated by MAPK activation and egr-1-dependent and -independent mechanisms. Am J Pathol. 2009;175:605–15.

CAS  PubMed  PubMed Central  Google Scholar 

Chen Q, Jiao J, Wang Y, et al. Egr-1 mediates low-dose arecoline induced human oral mucosa fibroblast proliferation via transactivation of Wnt5a expression. BMC Mol Cell Biol. 2020;21:80.

CAS  PubMed  PubMed Central  Google Scholar 

Xie B, Wang C, Zheng Z, et al. Egr-1 transactivates Bim gene expression to promote neuronal apoptosis. J Neurosci. 2011;31:5032–44.

CAS  PubMed  PubMed Central  Google Scholar 

Chang YC, Lii CK, Tai KW, Chou MY. Adverse effects of arecoline and nicotine on human periodontal ligament fibroblasts in vitro. J Clin Periodontol. 2001;28:277–82.

CAS  PubMed  Google Scholar 

Russell MA, Jarvis M, Iyer R, Feyerabend C. Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. Br Med J. 1980;280:972–6.

CAS  PubMed  PubMed Central  Google Scholar 

Benowitz NL. Nicotine and smokeless tobacco. CA Cancer J clin. 1988;38:244–7.

CAS  PubMed  Google Scholar 

Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57:79–115.

CAS  PubMed  Google Scholar 

Yang YH, Lien YC, Ho PS, et al. The effects of chewing areca/betel quid with and without cigarette smoking on oral submucous fibrosis and oral mucosal lesions. Oral Dis. 2005;11:88–94.

PubMed  Google Scholar 

Venkatesh D, Puranik RS, Vanaki SS, Puranik SR. Study of salivary arecoline in areca nut chewers. J Oral Maxillofac Pathol. 2018;22:446.

PubMed  PubMed Central  Google Scholar 

Vuga LJ, Ben-Yehudah A, Kovkarova-Naumovski E, et al. WNT5A is a regulator of fibroblast proliferation and resistance to apoptosis. Am J Respir Cell Mol Biol. 2009;41:583–9.

CAS  PubMed  PubMed Central  Google Scholar 

Choi JE, Kim JN, Jeong SH, Son SW. Nicotine induces the expression of early growth response-1 in human skin dermal fibroblasts. Int J Dermatol. 2010;49:158–61.

CAS  PubMed  Google Scholar 

Haider SM, Merchant AT, Fikree FF, Rahbar MH. Clinical and functional staging of oral submucous fibrosis. Br J Oral Maxillofac Surg. 2000;38:12–5.

CAS  PubMed  Google Scholar 

Chang YC, Hu CC, Tseng TH, et al. Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts. J Oral Pathol Med. 2001;30:458–64.

CAS  PubMed  Google Scholar 

Wollina U, Verma SB, Ali FM, Patil K. Oral submucous fibrosis: an update. Clin Cosmet Investig Dermatol. 2015;8:193–204.

PubMed  PubMed Central  Google Scholar 

Pindborg JJ, Chawla TN, Misra RK, Nagpaul RK, Gupta VK. Frequency of oral carcinoma, leukoplakia, leukokeratosis, leukoedema, submucous fibrosis, and lichen planus in 10,000 Indians in Lucknow, Uttar Pradesh, India; preliminary report. J Dent Res. 1965;44:61.

CAS  PubMed  Google Scholar 

Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol. 1966;22:764–79.

CAS  PubMed  Google Scholar 

Kim JW, Lim CW, Kim B. Effects of nicotine on corneal wound healing following acute alkali burn. PLoS ONE. 2017;12: e0179982.

PubMed  PubMed Central  Google Scholar 

Takeuchi-Igarashi H, Kubota S, Tachibana T, et al. Matrix remodeling response of human periodontal tissue cells toward fibrosis upon nicotine exposure. Odontology. 2016;104:35–43.

CAS  PubMed  Google Scholar 

Shieh DH, Chiang LC, Lee CH, Yang YH, Shieh TY. Effects of arecoline, safrole, and nicotine on collagen phagocytosis by human buccal mucosal fibroblasts as a possible mechanism for oral submucous fibrosis in Taiwan. J Oral Pathol Med. 2004;33:581–7.

CAS  PubMed  Google Scholar 

Jain G, Jaimes EA. Nicotine signaling and progression of chronic kidney disease in smokers. Biochem Pharmacol. 2013;86:1215–23.

CAS  PubMed  Google Scholar 

Guo L, Zhang Y, Lu J, et al. Nicotine promotes renal interstitial fibrosis via upregulation of XIAP in an alpha7-nAChR-dependent manner. Mol Cell Endocrinol. 2023;576: 111989.

CAS  PubMed  Google Scholar 

Chen H, Tao X, Cao H, et al. Nicotine exposure exacerbates silica-induced pulmonary fibrosis via STAT3-BDNF-TrkB-mediated epithelial-mesenchymal transition in alveolar type II cells. Food chemical toxicol An Int J Published Br Ind Biol Res Assoc. 2023;175: 113694.

CAS  Google Scholar 

Li Z, Lu D, Jin T, Liu X, Hao J. Nicotine facilitates pancreatic fibrosis by promoting activation of pancreatic stellate cells via alpha7nAChR-mediated JAK2/STAT3 signaling pathway in rats. Toxicol Lett. 2021;349:84–91.

CAS  PubMed  Google Scholar 

Zhang D, Dai J, Zhang M, et al. Paternal nicotine exposure promotes hepatic fibrosis in offspring. Toxicol Lett. 2021;343:44–55.

CAS  PubMed  Google Scholar 

Waters CM, Hancock DC, Evan GI. Identification and characterisation of the egr-1 gene product as an inducible, short-lived, nuclear phosphoprotein. Oncogene. 1990;5:669–74.

CAS  PubMed  Google Scholar 

Yu J, de Belle I, Liang H, Adamson ED. Coactivating factors p300 and CBP are transcriptionally crossregulated by Egr1 in prostate cells, leading to divergent responses. Mol Cell. 2004;15:83–94.

CAS  PubMed  Google Scholar 

Huang RP, Fan Y, Boynton AL. Uv irradiation upregulates Egr-1 expression at transcription level. J Cell Biochem. 1999;73:227–36.

CAS  PubMed  Google Scholar 

Hattori N, Nakagawa T, Yoneda M, et al. Compounds in cigarette smoke induce EGR1 expression via the AHR, resulting in apoptosis and COPD. J Biochem. 2022;172:365–76.

CAS  PubMed  Google Scholar 

Huang H, Ding C, Zhao WH, et al (2025). Nicotine promotes the progression and metastasis of non-small cell lung cancer by modulating the OTUB1-c-Myc-EZH2 axis. Acta Pharmacol Sin. https://doi.org/10.1038/s41401-025-01527-5.

Wang M, Li Y, Xiao Y, et al. Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer. Nat Commun. 2021;12:7006.

CAS  PubMed  PubMed Central  Google Scholar 

Rezvani K, Teng Y, De Biasi M. The ubiquitin-proteasome system regulates the stability of neuronal nicotinic acetylcholine receptors. J Mol Neurosci MN. 2010;40:177–84.

CAS