Cancer‐derived IgG involved in cisplatin resistance through PTP‐BAS/Src/PDK1/AKT signaling pathway

Wang, Luming; Gan, Ye‐Hua

doi:10.1111/odi.13583

Cited by 18 publications

(12 citation statements)

References 48 publications

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“…Generally, cancer-derived Ig is mainly detected in epithelial cancer cells, including those of breast cancer ( 12 – 15 ), colon cancer ( 16 , 17 ), cervical cancer ( 16 , 18 ), lung cancer ( 18 – 20 ), laryngeal cancer ( 21 ), nasopharyngeal cancer ( 22 ), pancreatic cancer ( 23 – 25 ), liver cancer ( 16 , 18 ), prostate cancer ( 26 – 28 ), oral cancer ( 29 , 30 ), thyroid cancer ( 31 ), parathyroid cancer ( 32 ), esophageal cancer ( 33 ), gastric cancer ( 34 ), renal cancer ( 35 ), and bladder cancer ( 36 ). At the subcellular level, cancer-derived Ig is mainly located in the cytoplasm and on the cell membrane.…”

Section: Wide Expression Of Ig In Cancer Cellsmentioning

confidence: 99%

Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

et al. 2021

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Traditionally, immunoglobulin (Ig) was believed to be produced by only B-lineage cells. However, increasing evidence has revealed a high level of Ig expression in cancer cells, and this Ig is named cancer-derived Ig. Further studies have shown that cancer-derived Ig shares identical basic structures with B cell-derived Ig but exhibits several distinct characteristics, including restricted variable region sequences and aberrant glycosylation. In contrast to B cell-derived Ig, which functions as an antibody in the humoral immune response, cancer-derived Ig exerts profound protumorigenic effects via multiple mechanisms, including promoting the malignant behaviors of cancer cells, mediating tumor immune escape, inducing inflammation, and activating the aggregation of platelets. Importantly, cancer-derived Ig shows promising potential for application as a diagnostic and therapeutic target in cancer patients. In this review, we summarize progress in the research area of cancer-derived Ig and discuss the perspectives of applying this novel target for the management of cancer patients.

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Section: Wide Expression Of Ig In Cancer Cellsmentioning

confidence: 99%

Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

et al. 2021

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“…In recent years, increasingly more researchers have found that tumor cells can produce IgG, known as cancer-derived immunoglobulin G (CIgG) [7,[19][20][21]. Many studies have shown that CIgG plays an important role in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

FCGRT, a cancer-derived immunoglobulin G binding protein, mediates the malignant phenotype of glioma

Yang

Wang

et al. 2022

Preprint

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CIgG has received increasing attention, and was first discovered by our group to indicate poor prognosis in glioma. Furthermore, by protein mass spectrometry, we found that FCGRT can combine with CIgG. However, the study of FCGRT in glioma has not been reported. We used the CGGA325, TCGA dataset and immunohistochemistry to verify the importance of FCGRT on the prognosis of glioma patients. Single cell sequencing data analysis evaluated that the role of FCGRT in the microenvironment of glioma. Estimate, ssGSEA, EPIC and xCell were used for immune infiltration analysis. FCGRT was knocked down in U251 cells to detect the effect of FCGRT on the malignant development of glioma. These results showed that patients with higher FCGRT expression had a shorter overall survival. FCGRT was closely related to the tumor microenvironment, especially to macrophages in the tumor microenvironment (r=0.743, p<0.001). Interestingly we also found that FCGRT was positively correlated with IGHG1. Finally, we found that knock-down of FCGRT resulted in a decrease in proliferation, migration and invasion of U251 cells. Taken together, we believe that FCGRT is an independent prognostic factor for glioma patients, and its possible mechanism is to promote proliferation and invasion of tumor cells by interacting with CIgG.

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Section: Discussionmentioning

confidence: 99%

“…Although cancer-IgG was discovered in cancer cells decades ago, previous studies mainly focused on the relationship between cancer-IgG and tumorigenesis. Wang and Gan (28) found that knockdown of cancer-IgG can regulate the PTP-BAS/Src/PDK1/ AKT pathway and thus significantly promote cisplatin-induced apoptosis and inhibition of oral squamous cell proliferation, migration, and invasion. Qin et al (9) found that, in prostate cancer, cancer-IgG staining was stronger in specimens at advanced clinical stages; androgen deprivation therapy for prostate cancer-induced cancer-IgG expression maintained stemness and facilitated cancer progression through mitogenactivated protein kinase/extracellular signal-regulated kinase Building upon previous research, this study first explored the role of cancer-IgG in tumor radiotherapy and found that it is possible to mediate radiotherapy resistance by modulating the PI3K/AKT/DNA-PKcs signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

High Expression of Cancer-IgG Is Associated With Poor Prognosis and Radioresistance via PI3K/AKT/DNA-PKcs Pathway Regulation in Lung Adenocarcinoma

et al. 2021

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BackgroundLung adenocarcinoma (LUAD) is the dominant type of lung neoplasms, and radiotherapy is its mainstay treatment, yet poor prognosis caused by radioresistance remains problematic. Cancer-derived immunoglobulin G (cancer-IgG) has been detected in multiple cancers and plays important roles in carcinogenesis. This study aimed to demonstrate that cancer-IgG is associated with poor prognosis of LUAD and to identify its role in radioresistance.MethodsCancer-IgG expression was detected by immunohistochemistry from 56 patients with stage III LUAD and by western blot and immunofluorescence in LUAD cell lines and in a human bronchial epithelial cell line. The effects of cancer-IgG silencing on the proliferation and apoptosis of PC9 and H292 cells were evaluated by plate cloning and apoptosis assay; the effects of cancer-IgG silencing on DNA damage repair ability and radiosensitivity were evaluated by colony-forming assay, γH2AX immunofluorescence, and neutral comet assay. Finally, we used the protein phosphorylation microarray and western blot to explore mechanisms involving cancer-IgG that increased radioresistance.ResultsCancer-IgG is widely expressed in stage III LUAD, and the overall survival and disease-free survival of patients with positive expression are notably lower than those of patients with negative expression, indicating the associations between cancer-IgG and poor prognosis as well as radioresistance. The expression of cancer-IgG in the four LUAD cell lines was located mainly on the cell membrane and cytoplasm and not in the normal lung epithelial cell. Knockdown of cancer-IgG in PC9 and H292 cells resulted in increased apoptosis and negatively affected cancer cell proliferation. After irradiation, silencing of cancer-IgG showed a decrease in colonies as well as increases in the Olive tail moment and γH2AX foci in nucleus, indicating that the knockdown of cancer-IgG resulted in a decrease in the damage repair ability of DNA double-strand breaks in LUAD cells and an enhanced radiosensitivity. The expression of p-AKT, p-GSK3β, and p-DNA-PKcs decreased in the knockdown group after radiotherapy, suggesting that cancer-IgG could affect radiotherapy resistance by mediating double-strand breaks damage repair in LUAD cells through the PI3K/AKT/DNA-PKcs pathway.ConclusionsThis study revealed that cancer-IgG regulates PI3K/AKT/DNA-PKcs signaling pathways to affect radioresistance of LUAD and associated with poor prognosis.

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Cancer‐derived IgG involved in cisplatin resistance through PTP‐BAS/Src/PDK1/AKT signaling pathway

Cited by 18 publications

References 48 publications

Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

FCGRT, a cancer-derived immunoglobulin G binding protein, mediates the malignant phenotype of glioma

High Expression of Cancer-IgG Is Associated With Poor Prognosis and Radioresistance via PI3K/AKT/DNA-PKcs Pathway Regulation in Lung Adenocarcinoma

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