Specific expression of MUC21 in micropapillary elements of lung adenocarcinomas – Implications for the progression of EGFR-mutated lung adenocarcinomas

Matsumura, Mai; Okihara, Koji; Nakashima, Yu; Mitsui, Hideaki; Denda-Nagai, Kaori; Suzuki, Tsuyoshi; Arai, Hiromasa; Umeda, Satoshi; Tateishi, Yoko; Koike, Chihiro; Kataoka, Toshiaki; Irimura, Tatsuro; Ohashi, Kenichi

doi:10.1371/journal.pone.0215237

Cited by 12 publications

(16 citation statements)

References 15 publications

(19 reference statements)

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“…MUC21, having a specific glycosylation status, may be involved in the progression of EGFR-mutated lung cancer, particularly at the stage where tumors are transforming from pure lepidic to micropapillary tumors through low papillary lepidic lesions (9). Specific expression of MUC21 in micropapillary elements of lung adenocarcinomas has been revealed, which suggests an associaton between MUC21 expression and the progression of EGFR-mutated lung adenocarcinomas (15). MUC21 inhibitors have potential to serve as drugs in the treatment of multiple types of cancers, such as lung cancer and esophageal carcinomas (15).…”

Section: Discussionmentioning

confidence: 97%

“…Specific expression of MUC21 in micropapillary elements of lung adenocarcinomas has been revealed, which suggests an associaton between MUC21 expression and the progression of EGFR-mutated lung adenocarcinomas (15). MUC21 inhibitors have potential to serve as drugs in the treatment of multiple types of cancers, such as lung cancer and esophageal carcinomas (15). However, the precise mechanism requires further study.…”

Section: Discussionmentioning

confidence: 99%

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MUC21 induces the viability and migration of glioblastoma via the STAT3/AKT pathway

Wang

Zhang

et al. 2022

Exp Ther Med

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Glioblastoma (GBM) is a malignant tumor with one of the fastest increasing morbidity and mortality rates. As such, more therapeutic targets need to be developed to combat this disease. Mucin 21 (MUC21) is a human counterpart of mouse epiglycanin and mediates multiple cellular functions. However, its possible effects on GBM and its possible mechanism remain unclear. The current study aimed to clarify the role or MUC21 in the progression of GBM by performing a series of in vitro assays, including Cell Counting Kit-8, colony formation, wound closure, transwell, and in vivo assays. In the present study, the aberrantly high expression of MUC21 in human GBM tissues and cell lines was observed and it was revealed that it was associated with the clinicopathological feature, tumor recurrence, in patients with GBM. MUC21 promoted the viability and motility of GBM cells in vitro and stimulated tumor growth in vivo. It was further confirmed that MUC21 promoted the progression of GBM via the STAT3/AKT pathway and it was considered that MUC21 could serve as a promising target for the treatment of GBM.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

MUC21 induces the viability and migration of glioblastoma via the STAT3/AKT pathway

Wang

Zhang

et al. 2022

Exp Ther Med

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“…Also, EGFR and KRAS (Kirsten Rat Sarcoma viral oncogene homolog) mutations and Hnf4α expression may participate in mucin expression profiles in these lung ADC subtypes ( 57 ). The overexpression of MUC21 proteins with a particular glycosylation state is implicated in developing EGFR -mutated lung ADCs associated with a high frequency of lymphatic vessels invasion and lymph node metastasis ( 58 ). Additionally, MUC5AC is linked to poor prognosis and would be a prospective therapeutic target in lung ADC due to its role in enhancing tumor heterogeneity with mucin production ( 59 ).…”

Section: Ecm-key Structural and Signaling Components Modulate Egfr Activation And Affect Cell Behavior Of Nsclcmentioning

confidence: 99%

EGFR-Dependent Extracellular Matrix Protein Interactions Might Light a Candle in Cell Behavior of Non-Small Cell Lung Cancer

Abdel-Mawgood

Ibrahim

2021

Front. Oncol.

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Lung cancer remains the leading cause of cancer-related death and is associated with a poor prognosis. Lung cancer is divided into 2 main types: the major in incidence is non-small cell lung cancer (NSCLC) and the minor is small cell lung cancer (SCLC). Although NSCLC progression depends on driver mutations, it is also affected by the extracellular matrix (ECM) interactions that activate their corresponding signaling molecules in concert with integrins and matrix metalloproteinases (MMPs). These signaling molecules include cytoplasmic kinases, small GTPases, adapter proteins, and receptor tyrosine kinases (RTKs), particularly the epidermal growth factor receptor (EGFR). In NSCLC, the interplay between ECM and EGFR regulates ECM stiffness, angiogenesis, survival, adhesion, migration, and metastasis. Furthermore, some tumor-promoting ECM components (e.g., glycoproteins and proteoglycans) enhance activation of EGFR and loss of PTEN. On the other hand, other tumor-suppressing glycoproteins and -proteoglycans can inhibit EGFR activation, suppressing cell invasion and migration. Therefore, deciphering the molecular mechanisms underlying EGFR and ECM interactions might provide a better understanding of disease pathobiology and aid in developing therapeutic strategies. This review critically discusses the crosstalk between EGFR and ECM affecting cell behavior of NSCLC, as well as the involvement of ECM components in developing resistance to EGFR inhibition.

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“…The results showed some alterations in adhesion molecules, basement membrane materials, and kinases 31 . In particular, overexpression of oligo‐glycosylated MUC21 protein 22 and amplification of chromosome 12q13‐21 locus covering CDK4 , MDM2 , and DYRK2 genes 31 were suggested to participate in producing micropapillary elements. Although there are no other studies that comprehensively compare molecular profiles between micropapillary and background lepidic (or papillary) elements in individual tumors, several studies have shown differences in molecular alterations (genetic mutations) between high‐grade and low‐grade components of LADCs (that were not specified as micropapillary) 28 .…”

Section: Tumor Progression In the Nonsmokers’ Pathwaymentioning

confidence: 99%

The nonsmokers’ and smokers’ pathways in lung adenocarcinoma: Histological progression and molecular bases

Okihara

Matsumura

Arai³

et al. 2021

Cancer Science

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There could be two carcinogenetic pathways for lung adenocarcinoma (LADC): the nonsmokers’ pathway and the smokers’ pathway. This review article describes the two pathways with special reference to potential relationships between histological subtypes, malignant grades, and driver mutations. The lung is composed of two different tissue units, the terminal respiratory unit (TRU) and the central airway compartment (CAC). In the nonsmokers’ pathway, LADCs develop from the TRU, and their histological appearances change from lepidic to micropapillary during the progression process. In the smokers’ pathway, LADCs develop from either the TRU or the CAC, and their histological appearances vary among cases in the middle of the progression process, but they are likely converged to acinar/solid at the end. On a molecular genetic level, the nonsmokers’ pathway is mostly driven by EGFR mutations, whereas in the smokers’ pathway, approximately one‐quarter of LADCs have KRAS mutations, but the other three‐quarters have no known driver mutations. p53 mutations are an important factor triggering the progression of both pathways, with unique molecular alterations associated with each, such as MUC21 expression and chromosome 12p13‐21 amplification in the nonsmokers’ pathway, and HNF4α expression and TTF1 mutations in the smokers’ pathway. However, investigation into the relationship between histological progression and genetic alterations is in its infancy. Tight cooperation between traditional histopathological examinations and recent molecular genetics can provide valuable insight to better understand the nature of LADCs.

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Specific expression of MUC21 in micropapillary elements of lung adenocarcinomas – Implications for the progression of EGFR-mutated lung adenocarcinomas

Cited by 12 publications

References 15 publications

MUC21 induces the viability and migration of glioblastoma via the STAT3/AKT pathway

MUC21 induces the viability and migration of glioblastoma via the STAT3/AKT pathway

EGFR-Dependent Extracellular Matrix Protein Interactions Might Light a Candle in Cell Behavior of Non-Small Cell Lung Cancer

The nonsmokers’ and smokers’ pathways in lung adenocarcinoma: Histological progression and molecular bases

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