ESRP1-regulated isoform switching of LRRFIP2 determines metastasis of gastric cancer

Lee, Ji Hee; Pang, Kyoungwha; Kim, Junil; Hong, Eunji; Lee, Jeeyun; Cho, Hee Jin; Park, Jinah; Son, Min Jung; Park, Sihyun; Lee, Minjung; Ooshima, Akira; Park, Jinah; Yang, Han–Kwang; Yang, Kyung‐Min; Kim, Seong-Jin

doi:10.1038/s41467-022-33786-9

Cited by 18 publications

(17 citation statements)

References 73 publications

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“…In addition, the splicing of specific genes such as CD44 has been shown to enhance the metastatic potential of cancer cells[ 61 - 63 ]. In addition, regulatory strategies to control AS in cancers, including metastatic liver cancer, remain largely unknown, suggesting gaps in our understanding of the underlying mechanisms[ 37 , 60 ]. In addition, associations between AS and metastatic phenotypes have been studied in various types of cancers, including colorectal and prostate cancers, suggesting that AS has a broader relevance in cancer metastasis[ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

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Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Geng,

Chen,

Chen

et al. 2024

World J Clin Oncol

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Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

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Section: Discussionmentioning

confidence: 99%

“…ESRP1 promotes liver metastasis in breast cancer cells by enhancing EMT[ 34 ]. ESRP1 regulates subtype conversion and determines gastric cancer metastasis[ 37 ]. ESRP1 drives AS of CD44 , thereby enhancing invasion and migration of epithelial ovarian cancer cells[ 38 ].…”

Section: Metastasis Mechanisms In Metastatic Liver Cancermentioning

confidence: 99%

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Geng,

Chen,

Chen

et al. 2024

World J Clin Oncol

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“…Similarly, a phase Ib/II trial (NCT02901301) conducted by Lee et al [123] evaluated the efficacy and safety of pembrolizumab associated with a first-line standard regimen in 43 patients. The chemotherapy regimen used was the combination of cisplatin and capecitabine.…”

Section: First Line Addition Of Immunotherapy To Standard First-line ...mentioning

confidence: 99%

HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies

Pous

Notario

Hierro

et al. 2023

IJMS

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Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10–20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, this being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody–drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

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“…Principal component analysis (PCA) with a published RNAseq data performed PCA on the union of the 8 DEG groups (Fig. 2A) on the new RNAseq data along with our previously published RNAseq data from the 18 gastric cancer cell lines, 18 gastric cancer tissue samples, and 16 normal gastric tissue samples (22,23). For the normalization between samples, we used scaled (z-transformed) log2 fragments per kilobase per million (FPKM).…”

Section: Transcriptome Data Analysismentioning

confidence: 99%

N-linked glycosylation is essential for anti-tumor activities of KIAA1324 in gastric cancer

Yun¹,

Hong

Kim

et al. 2023

Preprint

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KIAA1324 is a transmembrane protein reported largely as a tumor suppressor and favorable prognosis marker in various cancers, including gastric cancer. In this study, we report the role of N-linked glycosylation in KIAA1324 as a functional post-translational modification (PTM). Loss of N-linked glycosylation eliminated the potential of KIAA1324 to suppress cancer cell proliferation and migration. In addition, KIAA1324-mediated apoptosis and tumor regression were inhibited by the loss of N-linked glycosylation. The non-glycosylated mutant also showed altered localization and lost apoptotic activity by inhibiting the interaction between GRP78 and caspase 7. RNA sequencing analysis revealed that genes most relevant to the apoptosis and cell cycle arrest pathways were modulated by KIAA1324 with the N-linked glycosylation, and Gene Regulatory Network (GRN) analysis suggested novel targets of KIAA1324 for anti-tumor effects in transcription level. These data demonstrate that N-linked glycosylation of KIAA1324 is essential for the suppressive role of KIAA1324 protein in gastric cancer progression and indicates that KIAA1324 may have anti-tumor effects by targeting cancer-related genes with N-linked glycosylation. In conclusion, our study suggests the PTM of KIAA1324 is a necessary factor to consider for cancer prognosis and therapy improvement.

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ESRP1-regulated isoform switching of LRRFIP2 determines metastasis of gastric cancer

Cited by 18 publications

References 73 publications

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies

N-linked glycosylation is essential for anti-tumor activities of KIAA1324 in gastric cancer

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