» Articles » PMID: 31236545

Lgr6: From Stemness to Cancer Progression

Overview
Date 2019 Jun 26
PMID 31236545
Citations 5
Authors
Affiliations
Soon will be listed here.
Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide with poor prognosis, mainly due to the delay in the diagnosis. Adenocarcinoma, a subtype of non-small cell lung cancer, has the highest incidence and significant recurrence rates. Experimental and clinical researches suggested that the presence of cancer stem cells could support the development, malignization and resistance of lung cancer. Unfortunately, our knowledge in the field is still limited. Here we report our findings regarding a cell population expressing LGR6, an epithelial stem cell marker. Under the pressure of a fine regulated p38α MAPK/mir-17-92 axis, LGR6 stem cells produce differentiated bronchioalveolar cells, in the normal lung. LGR6 is enriched in tumour cells during adenocarcinoma progression. Similar to normal stem cells, LGR6 cancer cells show self-renewal and differentiation capacities, alongside with a higher oncogenic potential. Our studies suggest a disruption in the p38α MAPK/mir-17-92 network, that enhances Wnt pathway activity, could be responsible for the selection of malignant LGR6 tumour cells. These results support the existence of a cell population with stem-like characteristics and strong oncogenic potential. This population could be useful for predictive diagnosis and a novel target for improved and more effective therapies against metastases and recurrences of lung adenocarcinomas.

Citing Articles

The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer.

Sunaga N, Kaira K, Shimizu K, Tanaka I, Miura Y, Nakazawa S Thorac Cancer. 2023; 15(2):131-141.

PMID: 38014454 PMC: 10788478. DOI: 10.1111/1759-7714.15169.


BCL7B, a SWI/SNF complex subunit, orchestrates cancer immunity and stemness.

Higuchi S, Suehiro Y, Izuhara L, Yoshina S, Hirasawa A, Mitani S BMC Cancer. 2023; 23(1):811.

PMID: 37648998 PMC: 10466690. DOI: 10.1186/s12885-023-11321-3.


LGR6 promotes glioblastoma malignancy and chemoresistance by activating the Akt signaling pathway.

Cheng Y, Yang X, Gao X, Song S, Yang M, Xie F Exp Ther Med. 2021; 22(6):1364.

PMID: 34659510 PMC: 8515564. DOI: 10.3892/etm.2021.10798.


Individual DNA Methylation Pattern Shifts in Nanoparticles-Exposed Workers Analyzed in Four Consecutive Years.

Rossnerova A, Honkova K, Chvojkova I, Pelclova D, Zdimal V, Hubacek J Int J Mol Sci. 2021; 22(15).

PMID: 34360600 PMC: 8346047. DOI: 10.3390/ijms22157834.


CRISPR/Cas9-Mediated Foxp1 Silencing Restores Immune Surveillance in an Immunocompetent A20 Lymphoma Model.

Felce S, Anderson A, Maguire S, Gascoyne D, Armstrong R, Wong K Front Oncol. 2020; 10:448.

PMID: 32309216 PMC: 7145990. DOI: 10.3389/fonc.2020.00448.

References
1.
Giangreco A, Reynolds S, Stripp B . Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol. 2002; 161(1):173-82. PMC: 1850682. DOI: 10.1016/S0002-9440(10)64169-7. View

2.
Al-Hajj M, Wicha M, Benito-Hernandez A, Morrison S, Clarke M . Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003; 100(7):3983-8. PMC: 153034. DOI: 10.1073/pnas.0530291100. View

3.
Mucenski M, Wert S, Nation J, Loudy D, Huelsken J, Birchmeier W . beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis. J Biol Chem. 2003; 278(41):40231-8. DOI: 10.1074/jbc.M305892200. View

4.
Reya T, Clevers H . Wnt signalling in stem cells and cancer. Nature. 2005; 434(7035):843-50. DOI: 10.1038/nature03319. View

5.
Bender Kim C, Jackson E, Woolfenden A, Lawrence S, Babar I, Vogel S . Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005; 121(6):823-35. DOI: 10.1016/j.cell.2005.03.032. View