MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence

Gabasa, Marta; Radisky, Evette S.; Ikemori, Rafael; Bertolini, Giulia; Arshakyan, Marselina; Hockla, Alexandra; Duch, Paula; Rondinone, Ornella; Llorente, Alejandro; Maqueda, María; Davalos, Albert R.; Gavilán, Elena; Perera, Alexandre; Ramírez, Josep; Gascón, Pere; Reguart, Noemı́; Roz, Luca; Radisky, Derek C.; Alcaraz, Jordi

doi:10.1016/j.canlet.2021.01.028

Cited by 37 publications

(30 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases and are overexpressed in various malignant tumors. MMP1 promotes proliferation and drug resistance in many cancers, such as lung cancer [ 13 ], breast cancer [ 14 ], and head and neck cancer [ 15 ]. Therefore, targeting MMP1 is considered an important step in reversing drug resistance.…”

Section: Discussionmentioning

confidence: 99%

HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway

Jiao

et al. 2022

Cancers

View full text Add to dashboard Cite

Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene. However, recent reports have indicated that HPRT1 overexpression is associated with a poor prognosis in various types of cancers. Using The Cancer Genome Atlas (TCGA), HPRT1 was found to be highly expressed in various cancer types, especially in head and neck squamous cell carcinoma (HNSCC). Therefore, we measured HPRT1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between HPRT1 expression and clinical pathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC), a common type of HNSCC. We built OSCC cells with stable knockdown and overexpression of HPRT1 to observe its influence on chemoresistance and malignancy in vitro and vivo. We found that highly expressed HPRT1 was associated with a poor prognosis and could promote resistance to cisplatin (CDDP) in OSCC cells in both in vitro and in vivo. An RNA sequence assay was carried out to explore the mechanism of function of HPRT1, we found that HPRT1 could positively regulate the expression of MMP1 and the activation of the PI3K/AKT pathway, to regulate the resistance to CDDP of OSCC. In conclusion, HPRT1 can no longer be simply believed to be a housekeeping gene. HPRT1 overexpression indicates a worse prognosis and can improve CDDP resistance for patients with OSCC by promoting the MMP1/PI3K/Akt axis. HPRT1 may be a potential prognostic biomarker and therapeutic target in OSCC.

show abstract

Section: Discussionmentioning

confidence: 99%

HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway

Jiao

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…It is now clear that TAFs are molecularly and phenotypically heterogeneous in NSCLC and other solid tumors [16,17]. Yet recent work from our group supports that there is a dominant TAF phenotype in each histologic subtype [18][19][20], which accounts for the differential response to the antifibrotic drug nintedanib reported in TAFs in ADC and SCC in preclinical models [19,21] and validated in the LUME-1 trial in patients [22]. A deeper understanding of the epigenetic regulation of TAF phenotypes may shed light on their stability and potential interconvertibility [23], and may help in developing therapeutic strategies aiming to revert TAFs towards tumor-restraining phenotypes.…”

Section: Evidence That Tumor-associated Fibroblasts (Tafs) Are Epigenetically Reprogrammedmentioning

confidence: 87%

Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities

Alcaraz

Ikemori

Llorente

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer-related death worldwide. The desmoplastic stroma of lung cancer and other solid tumors is rich in tumor-associated fibroblasts (TAFs) exhibiting an activated/myofibroblast-like phenotype. There is growing awareness that TAFs support key steps of tumor progression and are epigenetically reprogrammed compared to healthy fibroblasts. Although the mechanisms underlying such epigenetic reprogramming are incompletely understood, there is increasing evidence that they involve interactions with either cancer cells, pro-fibrotic cytokines such as TGF-β, the stiffening of the surrounding extracellular matrix, smoking cigarette particles and other environmental cues. These aberrant interactions elicit a global DNA hypomethylation and a selective transcriptional repression through hypermethylation of the TGF-β transcription factor SMAD3 in lung TAFs. Likewise, similar DNA methylation changes have been reported in TAFs from other cancer types, as well as histone core modifications and altered microRNA expression. In this review we summarize the evidence of the epigenetic reprogramming of TAFs, how this reprogramming contributes to the acquisition and maintenance of a tumor-promoting phenotype, and how it provides novel venues for therapeutic intervention, with a special focus on lung TAFs.

show abstract

“…The IFI6 protein plays a central role in resistance to apoptosis in various cancer types [ 80 , 81 ], and MX1 protein levels are increased in lung adenocarcinoma [ 25 ]. Furthermore, it has been reported that MMP1, HMGA2, TRPA1 , and PLAU are highly expressed in various subtypes of lung cancer [ 26 – 28 , 31 – 34 , 43 , 44 , 49 – 51 ]. However, ISG15 , COL14A1 and HBG2 are mainly decreased in lung adenocarcinoma [ 30 , 64 , 70 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells

Hong

Jeong

Lee

et al. 2022

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Background Lung injury elicited by respiratory exposure to humidifier disinfectants (HDs) is known as HD-associated lung injury (HDLI). Current elucidation of the molecular mechanisms related to HDLI is mostly restricted to fibrotic and inflammatory lung diseases. In our previous report, we found that lung tumors were caused by intratracheal instillation of polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. However, the lung cancer-related genetic changes concomitant with the development of these lung tumors have not yet been fully defined. We aimed to discover the effect of long-term exposure of PHMG-p on normal human lung alveolar cells. Methods We investigated whether PHMG-p could increase distorted homeostasis of oncogenes and tumor-suppressor genes, with long-term and low-dose treatment, in human pulmonary alveolar epithelial cells (HPAEpiCs). Total RNA sequencing was performed with cells continuously treated with PHMG-p and harvested after 35 days. Results After PHMG-p treatment, genes with transcriptional expression changes of more than 2.0-fold or less than 0.5-fold were identified. Within 10 days of exposure, 2 protein-coding and 5 non-coding genes were selected, whereas in the group treated for 27–35 days, 24 protein-coding and 5 non-coding genes were identified. Furthermore, in the long-term treatment group, 11 of the 15 upregulated genes and 9 of the 14 downregulated genes were reported as oncogenes and tumor suppressor genes in lung cancer, respectively. We also found that 10 genes of the selected 24 protein-coding genes were clinically significant in lung adenocarcinoma patients. Conclusions Our findings demonstrate that long-term exposure of human pulmonary normal alveolar cells to low-dose PHMG-p caused genetic changes, mainly in lung cancer-associated genes, in a time-dependent manner.

show abstract

MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence

Cited by 37 publications

References 40 publications

HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway

HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway

Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities

Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells

Contact Info

Product

Resources

About