High FAS expression correlates with a better prognosis and efficacy of taxanes and target regents in breast cancer

Zhang, Yi; Shao, Xuan; Gao, Chenyi; Xu, Danying; Wu, Jun; Zhu, Xuan; Chen, Zhigang

doi:10.3233/cbm-203125

Cited by 3 publications

(5 citation statements)

References 26 publications

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“…All these genes whose expression is PIP-dependent are pro-apoptotic, which further confirms our conclusion on PIP as a pro-apoptotic molecule. Among these genes, only expression of FASLG and CD40 was linked to drug-resistance of BC cells 45 – 48 . These findings are, to some extent, in agreement with the data obtained by Debily et al 29 who conducted gene expression profiling and network analysis studies on several BC cell lines, including MDA-MB-231 and T47D.…”

Section: Discussionmentioning

confidence: 99%

Prolactin-induced protein (PIP) increases the sensitivity of breast cancer cells to drug-induced apoptosis

Urbaniak

Jabłońska

Suchański

et al. 2023

Sci Rep

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We have previously shown that high expression of prolactin-induced protein (PIP) correlates with the response of breast cancer (BC) patients to standard adjuvant chemotherapy (doxorubicin and cyclophosphamide), which suggests that the absence of this glycoprotein is associated with resistance of tumor cells to chemotherapy. Therefore, in the present study, we analyzed the impact of PIP expression on resistance of BC cells to anti-cancer drugs and its biological role in BC progression. Expression of PIP and apoptotic genes in BC cell lines was analyzed using real-time PCR and Western blotting. PIP was detected in BC tissue specimens using immunohistochemistry. The tumorigenicity of cancer cells was analyzed by the in vivo tumor growth assay. Apoptotic cells were detected based on caspase-3 activation, Annexin V binding and TUNEL assay. The interaction of PIP with BC cells was analyzed using flow cytometry. Using two cellular models of BC (i.e. T47D cells with the knockdown of the PIP gene and MDA-MB-231 cells overexpressing PIP), we found that high expression of PIP resulted in (1) increased sensitivity of BC cells to apoptosis induced by doxorubicin (DOX), 4-hydroperoxycyclophosphamide (4-HC), and paclitaxel (PAX), and (2) improved efficacy of anti-cancer therapy with DOX in the xenograft mice model. Accordingly, a clinical study revealed that BC patients with higher PIP expression were characterized by longer 5-year overall survival and disease-free survival. Subsequent studies showed that PIP up-regulated the expression of the following pro-apoptotic genes: CRADD, DAPK1, FASLG, CD40 and BNIP2. This pro-apoptotic activity is mediated by secreted PIP and most probably involves the specific surface receptor. This study demonstrates that a high expression level of PIP sensitizes BC cells to anti-cancer drugs. Increased sensitivity to chemotherapy is the result of pro-apoptotic activity of PIP, which is evidenced by up-regulation of specific pro-apoptotic genes. As high expression of PIP significantly correlated with a better response of patients to anti-cancer drugs, this glycoprotein can be a marker for the prognostic evaluation of adjuvant chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Prolactin-induced protein (PIP) increases the sensitivity of breast cancer cells to drug-induced apoptosis

Urbaniak

Jabłońska

Suchański

et al. 2023

Sci Rep

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“…Fas cell surface death receptor (FAS) has been found to play a critical role in the physiological regulation of programmed cell death as a member of TNF-receptor superfamily and has been implicated in the pathogenesis of several malignancies and immune system diseases ( Vandenabeele et al, 2010 ). FAS mRNA and protein expression levels were considerably lowered in breast carcinoma, whereas high FAS expression implies a better prognosis in breast cancer patients ( Zhang et al, 2021 ). FAS was demonstrated to be increased in tumor samples in our investigation, and its high expression in PTC patients predicted better survival, implying that FAS may be a tumor suppressor gene.…”

Section: Discussionmentioning

confidence: 99%

A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer

Wang

Shi

et al. 2022

Front. Genet.

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Background: Necroptosis, a type of programmed cell death, has been implicated in a variety of cancer-related biological processes. However, the roles of necroptosis-related genes in thyroid cancer yet remain unknown.Methods: A necroptosis-related gene signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis. The predictive value of the prognostic signature was validated in an internal cohort. Additionally, the single-sample gene set enrichment analysis (ssGSEA) was used to examine the relationships between necroptosis and immune cells, immunological functions, and immune checkpoints. Next, the modeled genes expressions were validated in 96 pairs of clinical tumor and normal tissue samples. Finally, the effects of modeled genes on PTC cells were studied by RNA interference approaches in vitro.Results: In this study, the risk signature of seven necroptosis-related genes was created to predict the prognosis of papillary thyroid cancer (PTC) patients, and all patients were divided into high-and low-risk groups. Patients in the high-risk group fared worse in terms of overall survival than those in the low-risk group. The area under the curve (AUC) of the receiving operating characteristic (ROC) curves proved the predictive capability of created signature. The risk score was found to be an independent risk factor for prognosis in multivariate Cox analysis. The lowrisk group showed increased immune cell infiltration and immunological activity, implying that they might respond better to immune checkpoint inhibitor medication. Next, GEO database and qRT-PCR in 96 pairs of matched tumorous and non-tumorous tissues were used to validate the expression of the seven modeled genes in PTCs, and the results were compatible with TCGA database. Finally, overexpression of IPMK, KLF9, SPATA2 could significantly inhibit the proliferation, invasion and migration of PTC cells. Conclusion:The created necroptosis associated risk signature has the potential to have prognostic capability in PTC for patient outcome. The findings of this study could pave the way for further research into the link between necroptosis and tumor immunotherapy.

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“…283,284 Loss of Fas expression is a major cause of poor prognosis and malignant progression in cancer patients. 285 In addition to participating in death receptor-mediated apoptosis, p53 can also induce mitochondria-dependent apoptosis by upregulating the expression level of Bax. 286,287 p53 can also promote the expression of various other Bcl-2 family proteins (such as NOXA, 288 PUMA, 289 etc.…”

Section: P53 Induces Apoptosismentioning

confidence: 99%

“…Low Fas expression results in loss of extrinsic pathway apoptosis signaling in various tumors, leading to malignant cancer progression 283,284 . Loss of Fas expression is a major cause of poor prognosis and malignant progression in cancer patients 285 …”

Section: Regulatory Mechanisms Of P53 On Downstream Genesmentioning

confidence: 99%

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Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Shen¹,

Wang²,

Mao³

et al. 2023

MedComm

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Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling‐targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor‐promoting role by blocking the mitochondria‐dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.

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High FAS expression correlates with a better prognosis and efficacy of taxanes and target regents in breast cancer

Cited by 3 publications

References 26 publications

Prolactin-induced protein (PIP) increases the sensitivity of breast cancer cells to drug-induced apoptosis

Prolactin-induced protein (PIP) increases the sensitivity of breast cancer cells to drug-induced apoptosis

A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

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