FABP7 inhibits proliferation and invasion abilities of cutaneous squamous cell carcinoma cells via the Notch signaling pathway

Sun,Zhonghui; Guo,Yunyi; Zhang,Danlu; Zhang,Guolong; Zhang,Ying; Wang,Xiuli

doi:10.3892/ol.2022.13374

FABP7 inhibits proliferation and invasion abilities of cutaneous squamous cell carcinoma cells via the Notch signaling pathway

Authors:
- Zhonghui Sun
- Yunyi Guo
- Danlu Zhang
- Guolong Zhang
- Ying Zhang
- Xiuli Wang
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Affiliations: Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200050, P.R. China, Department of Dermatology, Fengxian Institute of Dermatosis Prevention and Treatment, Shanghai 201408, P.R. China
Published online on: June 10, 2022 https://doi.org/10.3892/ol.2022.13374
Article Number: 254
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cutaneous squamous cell carcinoma (CSCC) is one of the most common non‑melanoma skin cancers worldwide. Fatty acid‑binding protein 7 (FABP7) has been reported to be involved in the occurrence, development, metastasis and prognosis of various tumors. In addition, downregulated FABP7 expression was demonstrated in cutaneous malignant melanoma in a previous study. Therefore, we speculated that FABP7 may be a biomarker for CSCC diagnosis. The aim of the present study was to determine the molecular mechanism underlying the effects of FABP7 in CSCC, which may provide a new diagnostic biomarker or treatment target for CSCC. Reverse transcription‑PCR, western blotting and immunohistochemistry assays were performed to detect the expression levels of FABP7 in CSCC tissues and cells. Overexpression of FABP7 was achieved in A431 and colo‑16 cell lines by transfection with an overexpression vector (oeFABP7). Cell proliferation, colony formation, migration and invasion were detected by Cell Counting Kit‑8, crystal violet, scratch and Transwell assays, respectively. Following FABP7 overexpression, western blotting was used to determine the expression levels of proliferation‑, invasion‑ and Notch pathway‑associated proteins, including Snail, N‑cadherin, Twist, matrix metalloproteinase (MMP)‑2, MMP‑7, Notch 1 and Notch 3. In addition a CSCC model in nude mice was constructed. Immunohistochemistry was used to determine the expression levels of FABP7, Ki67, Notch 1 and Notch 3. It was demonstrated that FABP7 expression levels were significantly reduced in human CSCC tissues and cells compared with normal samples. Overexpression of FABP7 inhibited the proliferation, invasion and migration abilities of A431 and colo‑16 cells compared with those in the negative control group. In addition, transfection with oeFABP7 reduced the expression levels of proliferation‑, invasion‑ and Notch pathway‑associated proteins compared with those in the negative control group. Overexpression of FABP7 also reduced the growth of CSCC tumors in vivo and inhibited the expression of Ki67, Notch 1 and Notch 3. Therefore, the results of the present study suggested that FABP7 may inhibit the proliferation and invasion of CSCC cells via the Notch signaling pathway.

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1	Llewellyn CD, Linklater K, Bell J, Johnson NW and Warnakulasuriya KA: Squamous cell carcinoma of the oral cavity in patients aged 45 years and under: A descriptive analysis of 116 cases diagnosed in the South East of England from 1990 to 1997. Oral Oncol. 39:106–114. 2003. View Article : Google Scholar : PubMed/NCBI
2	Vauterin TJ, Veness MJ, Morgan GJ, Poulsen MG and O'Brien CJ: Patterns of lymph node spread of cutaneous squamous cell carcinoma of the head and neck. Head Neck. 28:785–791. 2006. View Article : Google Scholar : PubMed/NCBI
3	Haytoglu NS, Gurel MS, Erdemir VA, Leblebici C and Haytoglu TG: An unusual case of sporotrichoid nodules: Metastatic cutaneous squamous cell carcinoma. Dermatol Online J. 19:181742013.PubMed/NCBI
4	Hahn SB, Kim DJ and Jeon CH: Clinical study of Marjolin's ulcer. Yonsei Med J. 31:234–241. 1990. View Article : Google Scholar : PubMed/NCBI
5	Zhao B: Clinical dermatology. Jiangsu Science and Technology Press; Nanjing: pp. p7072001
6	Aupperle KR, Boyle DL, Hendrix M, Seftor EA, Zvaifler NJ, Barbosa M and Firestein GS: Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor suppressor gene. Am J Pathol. 152:1091–1098. 1998.PubMed/NCBI
7	Sloane BF and Honn KV: Cysteine proteinases and metastasis. Cancer Metastasis Rev. 3:249–263. 1984. View Article : Google Scholar : PubMed/NCBI
8	Miwa S, Miyagawa S, Soeda J and Kawasaki S: Matrix metalloproteinase-7 expression and biologic aggressiveness of cholangiocellular carcinoma. Cancer. 94:428–434. 2002. View Article : Google Scholar : PubMed/NCBI
9	Zaravinos A, Kanellou P, Baritaki S, Bonavida B and Spandidos DA: BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma. Cell Cycle. 8:1402–1408. 2009. View Article : Google Scholar : PubMed/NCBI
10	Darido C, Georgy SR, Wilanowski T, Dworkin S, Auden A, Zhao Q, Rank G, Srivastava S, Finlay MJ, Papenfuss AT, et al: Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. Cancer Cell. 20:635–648. 2011. View Article : Google Scholar : PubMed/NCBI
11	Slipicevic A, Jørgensen K, Skrede M, Rosnes AK, Trøen G, Davidson B and Flørenes VA: The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells. BMC Cancer. 8:2762008. View Article : Google Scholar : PubMed/NCBI
12	Zhou J, Deng Z, Chen Y, Gao Y, Wu D, Zhu G, Li L, Song W, Wang X, Wu K and He D: Overexpression of FABP7 promotes cell growth and predicts poor prognosis of clear cell renal cell carcinoma. Urol Oncol. 33:113.e9–e17. 2015. View Article : Google Scholar : PubMed/NCBI
13	Umaru BA, Kagawa Y, Shil SK, Arakawa N, Pan Y, Miyazaki H, Kobayashi S, Yang S, Cheng A, Wang Y, et al: Ligand Bound fatty acid binding protein 7 (FABP7) drives melanoma cell proliferation via modulation of Wnt/β-catenin signaling. Pharm Res. 38:479–490. 2021. View Article : Google Scholar : PubMed/NCBI
14	Tani G, Tomuschat C, O'Donnell AM, Coyle D and Puri P: Increased population of immature enteric glial cells in the resected proximal ganglionic bowel of Hirschsprung's disease patients. J Surg Res. 218:150–155. 2017. View Article : Google Scholar : PubMed/NCBI
15	Goto Y, Koyanagi K, Narita N, Kawakami Y, Takata M, Uchiyama A, Nguyen L, Nguyen T, Ye X, Morton DL and Hoon DS: Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant melanoma. J Invest Dermatol. 130:221–229. 2010. View Article : Google Scholar : PubMed/NCBI
16	Hu YY, Zheng MH, Zhang R, Liang YM and Han H: Notch signaling pathway and cancer metastasis. Adv Exp Med Biol. 727:186–198. 2012. View Article : Google Scholar : PubMed/NCBI
17	Zhang W, Liu H, Liu Z, Zhu D, Amos CI, Fang S, Lee JE and Wei Q: Functional variants in notch pathway genes NCOR2, NCSTN, and MAML2 predict survival of patients with cutaneous melanoma. Cancer Epidemiol Biomarkers Prev. 24:1101–1110. 2015. View Article : Google Scholar : PubMed/NCBI
18	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
19	von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P and Snel B: STRING: A database of predicted functional associations between proteins. Nucleic Acids Res. 31:258–261. 2003. View Article : Google Scholar : PubMed/NCBI
20	Dressler F, Whalen JA, Reinhardt BN and Steere AC: Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 167:392–400. 1993. View Article : Google Scholar : PubMed/NCBI
21	Cañueto J, Cardeñoso E, Garcia J, Santos-Briz A, Castellanos A, Fernández-López E, Blanco-Gómez A, Perez-Losada J and Román-Curto C: EGFR expression is associated with poor outcome in cutaneous squamous cell carcinoma. Br J Dermatol. 176:279–1287. 2017. View Article : Google Scholar : PubMed/NCBI
22	Wu C, Bain X, Zhang L, Hu Y, Wu Y, Pei T and Han X: Long noncoding RNA LINC00968 inhibits proliferation, migration and invasion of lung adenocarcinoma through targeting miR-22-5p/CDC14A axis. 3 Biotech. 11:4332021. View Article : Google Scholar : PubMed/NCBI
23	Liang Y, Bollen AW, Aldape KD and Gupta N: Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 6:972006. View Article : Google Scholar : PubMed/NCBI
24	Tripathi S, Kushwaha R, Mishra J, Gupta MK, Kumar H, Sanyal S, Singh D, Sanyal S, Sahasrabuddhe AA, Kamthan M, et al: Docosahexaenoic acid up-regulates both PI3K/AKT-dependent FABP7-PPARγ interaction and MKP3 that enhance GFAP in developing rat brain astrocytes. J Neurochem. 140:96–113. 2017. View Article : Google Scholar : PubMed/NCBI
25	Nijsten T, Geluyckens E, Colpaert C and Lambert J: Peroxisome proliferator-activated receptors in squamous cell carcinoma and its precursors. J Cutan Pathol. 32:340–347. 2005. View Article : Google Scholar : PubMed/NCBI
26	Man MQ, Barish GD, Schmuth M, Crumrine D, Barak Y, Chang S, Jiang Y, Evans RM, Elias PM and Feingold KR: Deficiency of PPARbeta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation. J Invest Dermatol. 128:370–377. 2008. View Article : Google Scholar : PubMed/NCBI
27	Agelopoulos K, Rülander F, Dangelmaier J, Lotts T, Osada N, Metze D, Luger TA, Loser K and Ständer S: Neurokinin 1 receptor antagonists exhibit peripheral effects in prurigo nodularis including reduced ERK1/2 activation. J Eur Acad Dermatol Venereol. 33:2371–2379. 2019. View Article : Google Scholar : PubMed/NCBI
28	Luo Q, Li W, Zhao T, Tian X, Liu Y and Zhang X: Role of miR-148a in cutaneous squamous cell carcinoma by repression of MAPK pathway. Arch Biochem Biophys. 583:47–54. 2015. View Article : Google Scholar : PubMed/NCBI
29	Sun Y, Tu Y, He LI, Ji C and Cheng BO: High mobility group box 1 regulates tumor metastasis in cutaneous squamous cell carcinoma via the PI3K/AKT and MAPK signaling pathways. Oncol Lett. 11:59–62. 2016. View Article : Google Scholar : PubMed/NCBI
30	Piipponen M, Nissinen L, Farshchian M, Riihilä P, Kivisaari A, Kallajoki M, Peltonen J, Peltonen S and Kähäri VM: Long noncoding RNA PICSAR promotes growth of cutaneous squamous cell carcinoma by regulating ERK1/2 activity. J Invest Dermatol. 136:1701–1710. 2016. View Article : Google Scholar : PubMed/NCBI
31	Yamane K, Jinnin M, Etoh T, Kobayashi Y, Shimozono N, Fukushima S, Masuguchi S, Maruo K, Inoue Y, Ishihara T, et al: Down-regulation of miR-124/-214 in cutaneous squamous cell carcinoma mediates abnormal cell proliferation via the induction of ERK. J Mol Med (Berl). 91:69–81. 2013. View Article : Google Scholar : PubMed/NCBI
32	Karbowniczek M, Chosia M and Domagała W: Nuclear morphometry of MIB-1 positive and negative tumor cells in primary and metastatic malignant melanoma of the skin. Pol J Pathol. 50:235–241. 1999.PubMed/NCBI
33	Pourreyron C, Chen M, McGrath JA, Salas-Alanis JC, South AP and Leigh IM: High levels of type VII collagen expression in recessive dystrophic epidermolysis bullosa cutaneous squamous cell carcinoma keratinocytes increases PI3K and MAPK signalling, cell migration and invasion. Br J Dermatol. 170:1256–1265. 2014. View Article : Google Scholar : PubMed/NCBI
34	Luo Y, Wang Q, Tian P and Jia Y: Highly expressed CHAF1A and PCNA are positively associated with malignancy of cervical squamous cell carcinoma. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 33:1696–1701. 2017.(In Chinese). PubMed/NCBI
35	Gong X, Tao Y, Zhou L, Yu L, Wu S, Song W, Wang D and Cheng Z: Expressions of Snail, Slug and KAI1 proteins in cervical carcinoma and their clinicopathological significance. Nan Fang Yi Ke Da Xue Xue Bao. 35:1733–1738. 2015.(In Chinese). PubMed/NCBI
36	Yao J, Caballero OL, Huang Y, Lin C, Rimoldi D, Behren A, Cebon JS, Hung MC, Weinstein JN, Strausberg RL and Zhao Q: Altered expression and splicing of ESRP1 in malignant melanoma correlates with epithelial-mesenchymal status and tumor-associated immune cytolytic activity. Cancer Immunol Res. 4:552–561. 2016. View Article : Google Scholar : PubMed/NCBI
37	Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC and Wu KJ: Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol. 10:295–305. 2008. View Article : Google Scholar : PubMed/NCBI
38	Ahmed Haji Omar A, Haglund C, Virolainen S, Häyry V, Atula T, Kontio R, Salo T, Sorsa T and Hagström J: MMP-7, MMP-8, and MMP-9 in oral and cutaneous squamous cell carcinomas. Oral Surg Oral Med Oral Pathol Oral Radiol. 119:459–467. 2015. View Article : Google Scholar : PubMed/NCBI
39	Toland AE: Frequent somatic mutations of chromatin remodeling genes in metastatic cutaneous squamous cell carcinoma. Dermatol Online J. 22:2016.