Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer

Oshi, Masanori; Tokumaru, Yoshihisa; Mukhopadhyay, Swagoto; Yan, Li; Matsuyama, Ryusei; Endo, Itaru; Takabe, Kazuaki

doi:10.3390/cells10030653

Cited by 37 publications

(28 citation statements)

References 53 publications

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“…For example, ANXA1 has tumor suppressor roles in prostate, oral squamous cell [29] and head and neck cancer [30]. On the contrary, ANXA1 has tumor promoter roles in pancreatic cancer [31], breast cancer [32], liver cancer [33], lung cancer [34], thyroid cancer [24] and esophageal cancer [35]. Our study results add another piece of evidence that ANXA1 plays various roles in different cancer types and its complex regulation mechanisms.…”

Section: Discussionmentioning

confidence: 51%

The Association of Annexin A1 and Chemosensitivity to Osimertinib in Lung Cancer Cells

Chuang

Lung

Chen

et al. 2021

Cancers

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Annexin A1 (ANXA1) has been reported to promote tumor growth and resistance to chemotherapy drugs in lung cancer cells. In this study, we focused on the association of ANXA1 and chemosensitivity with a third generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), Osimertinib, in lung cancer cells with EGFR mutations. The overexpression of ANXA1 was observed in the lung cancer cells studied. The downregulation of ANXA1 with small interference RNA (siRNA) decreased the growth of lung cancer cells. In lung cancer cells with EGFR mutations, the knockdown of ANXA1 increased the chemosensitivity to Osimertinib, and decreased the tumorigenesis, invasion and migration of lung cancer cells. Further study showed that the knockdown of ANXA1 inhibited the phosphorylation of EGFR and down-stream Akt pathways and promoted apoptosis in lung cancer cells treated with Osimertinib. A mice xenograft lung cancer model was established in our study and showed that ANXA1 siRNA enhanced the effects of Osimertinib in vivo. Our study results showed that ANXA1 plays critical roles in chemosensitivity to EGFR-TKI in lung cancer cells with the EGFR mutation. Our efforts may be used in the development of lung cancer treatment strategies in the future.

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Section: Discussionmentioning

confidence: 51%

The Association of Annexin A1 and Chemosensitivity to Osimertinib in Lung Cancer Cells

Chuang

Lung

Chen

et al. 2021

Cancers

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“…The activity of UPR was quantified as the degree of enrichment of the "HALLMARK_UNFOLDED_PROTEIN_ RESPONSE" gene set (Table S1 lists all the genes included in this gene set) defined and generated as one of the Hallmark gene set collections of the Molecular Signatures Database (MSigDB) [20] using the gene set variation analysis (GSVA) algorithm [21] in the Bioconductor package (version 3.10). We have previously reported the clinical relevance of multiple signaling pathways and responses using a similar approach [12][13][14][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39].…”

Section: Methodsmentioning

confidence: 99%

The Unfolded Protein Response Is Associated with Cancer Proliferation and Worse Survival in Hepatocellular Carcinoma

Patel

Oshi

Yan

et al. 2021

Cancers

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Hepatocellular carcinoma is a leading cause of cancer death worldwide. The unfolded protein response (UPR) has been revealed to confer tumorigenic capacity in cancer cells. We hypothesized that a quantifiable score representative of the UPR could be used as a biomarker for cancer progression in HCC. In this study, a total of 655 HCC patients from 4 independent HCC cohorts were studied to examine the relationships between enhancement of the UPR and cancer biology and patient survival in HCC utilizing an UPR score. The UPR correlated with carcinogenic sequence and progression of HCC consistently in two cohorts. Enhanced UPR was associated with the clinical parameters of HCC progression, such as cancer stage and multiple parameters of cell proliferation, including histological grade, mKI67 gene expression, and enrichment of cell proliferation-related gene sets. The UPR was significantly associated with increased mutational load, but not with immune cell infiltration or angiogeneis across independent cohorts. The UPR was consistently associated with worse survival across independent cohorts of HCC. In conclusion, the UPR score may be useful as a biomarker to predict prognosis and to better understand HCC.

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“…Accordingly, a deficiency in FPR2 has been related to a sustained polarization toward an M1 phenotype in hepatocellular carcinoma [ 216 ]. Moreover, the role of AnxA1 in inducing TH2 cells infiltration in pancreatic cancer [ 235 ] and in inducing the differentiation and expansion of Tregs in the TME of triple-negative breast cancer models has also been described [ 100 ]. Bai and collaborators showed that the proliferation of effector T cells, when treated with Ac2-26, was lower and that the function of Tregs was impaired when these cells were treated with the FPR inhibitor Boc1.…”

Section: Structure and Functions Of Annexin A1mentioning

confidence: 99%

Annexin A1 as a Regulator of Immune Response in Cancer

Araújo

Mota

Ferreira

et al. 2021

Cells

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Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the N-terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.

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Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer

Cited by 37 publications

References 53 publications

The Association of Annexin A1 and Chemosensitivity to Osimertinib in Lung Cancer Cells

The Association of Annexin A1 and Chemosensitivity to Osimertinib in Lung Cancer Cells

The Unfolded Protein Response Is Associated with Cancer Proliferation and Worse Survival in Hepatocellular Carcinoma

Annexin A1 as a Regulator of Immune Response in Cancer

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