Integrins, the receptors of the extracellular matrix, are critical in the proliferation and metastasis of cancer cells. GMI, a Ganoderma microsporum immunomodulatory protein, possesses anticancer and antivirus abilities. The object of this study is to investigate the role of GMI in the integrins signaling pathway in lung cancer cells that harbor the EGFR L858R/T790M double mutation and osimertinib‐resistance. Liquid chromatography‐mass spectrometry and western blot assay were used to investigate the effect of GMI on inhibiting the protein expressions of integrins in H1975 cells. The migration ability and xenograft tumor growth of H1975 were suppressed by GMI. To elucidate the role of the integrin family in lung cancer resistant to osimertinib (AZD‐9291, Tagrisso), H1975 cells were used to establish the osimertinib‐resistant cells, named H1975/TR cells. The expressions of Integrin αV and stemness markers were much higher in H1975/TR cells than in H1975 cells. GMI suppressed cell viability, tumor spheroid growth, and the expressions of integrin αV and β1 in H1975/TR cells. Furthermore, GMI suppressed the expressions of stemness markers and formation of tumor spheres via blocking integrin αV signaling cascade. This is the first study to reveal the novel function of GMI in constraining cancer stem cells and migration by abolishing the integrin αV‐related signaling pathway in EGFR‐mutated and osimertinib‐resistant lung cancer cells.

中文翻译：

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灵芝小孢子免疫调节蛋白 GMI 对整合素 αV 的抑制消除了对奥希替尼耐药的 EGFR 突变肺癌细胞的干性和迁移


整合素是细胞外基质的受体，在癌细胞的增殖和转移中起着关键作用。GMI 是一种灵芝小孢子免疫调节蛋白，具有抗癌和抗病毒能力。本研究的目的是研究 GMI 在携带 EGFR L858R/T790M 双突变和奥希替尼耐药的肺癌细胞整合素信号通路中的作用。采用液相色谱-质谱法和 western blot 法研究 GMI 对抑制 H1975 细胞整合素蛋白表达的影响。GMI 抑制 H1975 的迁移能力和异种移植肿瘤生长。为了阐明整合素家族在奥希替尼耐药肺癌 （AZD-9291， Tagrisso） 中的作用，使用 H1975 细胞建立奥希替尼耐药细胞，称为 H1975/TR 细胞。H1975/TR 细胞中整合素 αV 和干性标志物的表达远高于 H1975 细胞。GMI 抑制 H1975/TR 细胞中细胞活力、肿瘤球状体生长以及整合素 αV 和 β1 的表达。此外，GMI 通过阻断整合素 αV 信号级联反应抑制干性标志物的表达和肿瘤球体的形成。这是第一项通过消除 EGFR 突变和奥希替尼耐药肺癌细胞中整合素 αV 相关信号通路来揭示 GMI 在限制癌症干细胞和迁移方面的新功能的研究。