Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

Nenghong YANG; Likun REN; She TIAN; Min HAN; Zhu LI; Yuxiang ZHAO; Peng LIU

doi:10.12449/JCH250219

Volume 41 Issue 2

Feb. 2025

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Article Navigation > Journal of Clinical Hepatology > 2025 > 41(2): 322-332

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Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

DOI: 10.12449/JCH250219

1.
Department of Hepatobiliary Surgery，The Affiliated Hospital of Guizhou Medical University，Guiyang 550000，China
2.
Clinical School of Medicine，Guizhou Medical University，Guiyang 550000，China

Research funding:

Guizhou Provincial Science and Technology Program (QKH-JC2024-ZK［2024］230);

Guizhou Provincial Health Commission Science and Technology Fund Project (gzwkj2024-373)

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Corresponding author: LIU Peng， liupeng5061@126.com （ORCID： 0000-0003-0471-3836）
Received Date: 2024-06-05
Accepted Date: 2024-07-11
Published Date: 2025-02-25

Abstract

Abstract

Objective To investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. Methods A comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. Results The analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. Conclusion LAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.
- Pancreatic Neoplasms,
- Laminin,
- Epithelial-Mesenchymal Transition,
- Neoplasm Invasiveness,
- Neoplasm Metastasis

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References

[1]	HALBROOK CJ, LYSSIOTIS CA, PASCA DI MAGLIANO M, et al. Pancreatic cancer: Advances and challenges[J]. Cell, 2023, 186( 8): 1729- 1754. DOI: 10.1016/j.cell.2023.02.014.
[2]	GAIANIGO N, MELISI D, CARBONE C. EMT and treatment resistance in pancreatic cancer[J]. Cancers, 2017, 9( 9): 122. DOI: 10.3390/cancers9090122.
[3]	FRIEND C, PARAJULI P, RAZZAQUE MS, et al. Deciphering epithelial-to-mesenchymal transition in pancreatic cancer[J]. Adv Cancer Res, 2023, 159: 37- 73. DOI: 10.1016/bs.acr.2023.02.008.
[4]	KECHAGIA Z, SÁEZ P, GÓMEZ-GONZÁLEZ M, et al. The laminin-keratin link shields the nucleus from mechanical deformation and signalling[J]. Nat Mater, 2023, 22( 11): 1409- 1420. DOI: 10.1038/s41563-023-01657-3.
[5]	TAYEM R, NIEMANN C, PESCH M, et al. Laminin 332 is indispensable for homeostatic epidermal differentiation programs[J]. J Invest Dermatol, 2021, 141( 11): 2602- 2610. e 3. DOI: 10.1016/j.jid.2021.04.008.
[6]	O’CONNELL P. Of LAMA3 and LAMB3: A novel gene therapy for epidermolysis bullosa[J]. Mol Ther, 2024, 32( 5): 1197- 1198. DOI: 10.1016/j.ymthe.2024.04.014.
[7]	YAMASHITA H, TRIPATHI M, HARRIS MP, et al. The role of a recombinant fragment of laminin-332 in integrin alpha3beta1-dependent cell binding, spreading and migration[J]. Biomaterials, 2010, 31( 19): 5110- 5121. DOI: 10.1016/j.biomaterials.2010.03.003.
[8]	ZENZO GD, HACHEM ME, DIOCIAIUTI A, et al. A truncating mutation in the laminin-332α chain highlights the role of the LG45 proteolytic domain in regulating keratinocyte adhesion and migration[J]. Br J Dermatol, 2014, 170( 5): 1056- 1064. DOI: 10.1111/bjd.12816.
[9]	TOMCZAK K, CZERWIŃSKA P, WIZNEROWICZ M. The Cancer Genome Atlas(TCGA): An immeasurable source of knowledge[J]. Contemp Oncol, 2015, 19( 1A): A68- A77. DOI: 10.5114/wo.2014.47136.
[10]	SUBRAMANIAN A, TAMAYO P, MOOTHA VK, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles[J]. Proc Natl Acad Sci U S A, 2005, 102( 43): 15545- 15550. DOI: 10.1073/pnas.0506580102.
[11]	CARITHERS LJ, MOORE HM. The genotype-tissue expression(GTEx) project[J]. Biopreserv Biobank, 2015, 13( 5): 307- 308. DOI: 10.1089/bio.2015.29031.hmm.
[12]	BARRETT T, WILHITE SE, LEDOUX P, et al. NCBI GEO: Archive for functional genomics data sets: Update[J]. Nucleic Acids Res, 2013, 41( Database issue): D991- D995. DOI: 10.1093/nar/gks1193.
[13]	UHLEN M, ZHANG C, LEE S, et al. A pathology atlas of the human cancer transcriptome[J]. Science, 2017, 357( 6352): eaan2507. DOI: 10.1126/science.aan2507.
[14]	HUANG CQ, CHEN J. Laminin-332 mediates proliferation, apoptosis, invasion, migration and epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma[J]. Mol Med Rep, 2021, 23( 1): 11. DOI: 10.3892/mmr.2020.11649.
[15]	TRAUB B, LINK KH, KORNMANN M. Curing pancreatic cancer[J]. Semin Cancer Biol, 2021, 76: 232- 246. DOI: 10.1016/j.semcancer.2021.05.030.
[16]	PARK W, CHAWLA A, O’REILLY EM. Pancreatic cancer: A review[J]. JAMA, 2021, 326( 9): 851- 862. DOI: 10.1001/jama.2021.13027.
[17]	DERYNCK R, WEINBERG RA. EMT and cancer: More than meets the eye[J]. Dev Cell, 2019, 49( 3): 313- 316. DOI: 10.1016/j.devcel.2019.04.026.
[18]	PALAMARIS K, FELEKOURAS E, SAKELLARIOU S. Epithelial to mesenchymal transition: Key regulator of pancreatic ductal adenocarcinoma progression and chemoresistance[J]. Cancers, 2021, 13( 21): 5532. DOI: 10.3390/cancers13215532.
[19]	SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2016[J]. CA Cancer J Clin, 2016, 66( 1): 7- 30. DOI: 10.3322/caac.21332.
[20]	LI DD, XIA LY, HUANG P, et al. Heterogeneity and plasticity of epithelial-mesenchymal transition(EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms[J]. Cell Prolif, 2023, 56( 6): e13423. DOI: 10.1111/cpr.13423.
[21]	REN H, DU PZ, GE ZY, et al. TWIST1 and BMI1 in cancer metastasis and chemoresistance[J]. J Cancer, 2016, 7( 9): 1074- 1080. DOI: 10.7150/jca.14031.
[22]	PAUL MC, SCHNEEWEIS C, FALCOMATÀ C, et al. Non-canonical functions of SNAIL drive context-specific cancer progression[J]. Nat Commun, 2023, 14( 1): 1201. DOI: 10.1038/s41467-023-36505-0.
[23]	WEI T, ZHANG XY, ZHANG Q, et al. Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer[J]. Cancer Lett, 2019, 452: 237- 243. DOI: 10.1016/j.canlet.2019.03.009.
[24]	MALTSEVA DV, RODIN SA. Laminins in metastatic cancer[J]. Mol Biol, 2018, 52( 3): 411- 434. DOI: 10.7868/S0026898418030059.
[25]	ROUSSELLE P, SCOAZEC JY. Laminin 332 in cancer: When the extracellular matrix turns signals from cell anchorage to cell movement[J]. Semin Cancer Biol, 2020, 62: 149- 165. DOI: 10.1016/j.semcancer.2019.09.026.
[26]	NING BS, MEI YE. LAMA3 promotes tumorigenesis of oral squamous cell carcinoma by METTL3-mediated N6-methyladenosine modification[J]. Crit Rev Immunol, 2024, 44( 2): 49- 59. DOI: 10.1615/CritRevImmunol.2023051066.
[27]	ISLAM K, BALASUBRAMANIAN B, VENKATRAMAN S, et al. Upregulated LAMA3 modulates proliferation, adhesion, migration and epithelial-to-mesenchymal transition of cholangiocarcinoma cells[J]. Sci Rep, 2023, 13( 1): 22598. DOI: 10.1038/s41598-023-48798-8.
[28]	FENG LY, HUANG YZ, ZHANG W, et al. LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer[J]. J Ovarian Res, 2021, 14( 1): 67. DOI: 10.1186/s13048-021-00807-y.

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沈阳化工大学材料科学与工程学院沈阳 110142

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Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

DOI: 10.12449/JCH250219

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Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

DOI: 10.12449/JCH250219

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