Data from Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance

Uchihara, Tomoyuki; Miyake, Keisuke; Yonemura, Atsuko; Komohara, Yoshihiro; Itoyama, Rumi; Koiwa, Mayu; Yasuda, Tadahito; Arima, Kei; Harada, Kazuto; Eto, Kojiro; Hayashi, Hiromitsu; Iwatsuki, Masaaki; Iwagami, Shiro; Baba, Yoshifumi; Yoshida, Naoya; Yashiro, Masakazu; Masuda, Mari; Ajani, Jaffer A.; Tan, Patrick; Baba, Hideo; Ishimoto, Takatsugu

doi:10.1158/0008-5472.c.6511711.v1

Cited by 1 publication

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“…However, how to change the biological function by ITGB1 needs further study. Consistently, the integrin family was implicated as an important inducer of tumorigenesis, and it was significantly implicated in cancer metastasis (81), drug resistance (82), and immune evasion (83), and it was clear that ITGB1 was one of the most important integrin family members. In terms of metabolism, current studies have shown that integrin activity can regulate insulin sensitivity in adipocytes and thereby systemic metabolism (84).…”

Section: B Amentioning

confidence: 90%

ITGB1-mediated molecular landscape and cuproptosis phenotype induced the worse prognosis in diffuse gastric cancer

Zhu

Chen

Han³

et al. 2023

Front. Oncol.

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Diffuse type gastric cancer was identified with relatively worse prognosis than other Lauren’s histological classification. Integrin β1 (ITGB1) was a member of integrin family which played a markedly important role in tumorigenesis and progression. However, the influence of ITGB1 in diffuse gastric cancer (DGC) remains uncertain. Here, we leveraged the transcriptomic and proteomic data to explore the association between ITGB1 expression and clinicopathologic information and biological process in DGC. Cell phenotype experiments combined with quantitative-PCR (q-PCR) and western blotting were utilized to identify the potential molecular mechanism underling ITGB1.Transcriptomics and proteomics both revealed that the higher ITGB1 expression was significantly associated with worse prognosis in DGC, but not in intestinal GC. Genomic analysis indicated that the mutation frequency of significantly mutated genes of ARID1A and COL11A1, and mutational signatures of SBS6 and SBS15 were markedly increased in the ITGB1 low expression subgroup. The enrichment analysis revealed diverse pathways related to dysregulation of ITGB1 in DGC, especially in cell adhesion, proliferation, metabolism reprogramming, and immune regulation alterations. Elevated activities of kinase-ROCK1, PKACA/PRKACA and AKT1 were observed in the ITGB1 high-expression subgroup. The ssGSEA analysis also found that ITGB1 low-expression had a higher cuproptosis score and was negatively correlated with key regulators of cuproptosis, including FDX1, DLAT, and DLST. We further observed that the upregulated expression of mitochondrial tricarboxylic acid (TCA) cycle in the ITGB1 low-expression group. Reduced expression of ITGB1 inhibited the ability of cell proliferation and motility and also potentiated the cell sensitive to copper ionophores via western blotting assay. Overall, this study revealed that ITGB1 was a protumorigenic gene and regulated tumor metabolism and cuproptosis in DGC.

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