Proteomic Profile of Sorafenib Resistance in Hepatocellular Carcinoma; GRP78 Expression Is Associated With Inferior Response to Sorafenib

Feng, Yin‐Hsun; Tung, Chao‐Ling; Su, Yu‐Chu; Tsao, Chao‐Jung; Wu, Tingfeng

doi:10.21873/cgp.20159

Cited by 15 publications

(11 citation statements)

References 29 publications

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“…These studies suggest that targeting GRP78 for the treatment of cancer is unlikely to have major deleterious side effects [ 31 , 47 , 48 , 49 ]. An elevated GRP78 level has been linked to the acquired resistance of cancer cells to tamoxifen [ 50 ], 5-fluorouracil (5-FU) [ 51 ], gemcitabine [ 52 ], and targeted therapy agents such as sorafenib [ 53 ] and sunitinib [ 54 ]. Regarding the marked effect of the FO and Se combination on GRP78 reduction shown in this study, this combination might have potential in relieving other GRP78-associated treatment resistances of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Omega-3 Fatty Acid-Enriched Fish Oil and Selenium Combination Modulates Endoplasmic Reticulum Stress Response Elements and Reverses Acquired Gefitinib Resistance in HCC827 Lung Adenocarcinoma Cells

et al. 2020

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Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated β-catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Omega-3 Fatty Acid-Enriched Fish Oil and Selenium Combination Modulates Endoplasmic Reticulum Stress Response Elements and Reverses Acquired Gefitinib Resistance in HCC827 Lung Adenocarcinoma Cells

et al. 2020

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“…In HCC tumors from patients treated with sorafenib, 73% showed high GRP78 expression, which was associated with the shortest progression-free survival ( 41 ). Elevated GRP78 is also proposed as a predictive biomarker in HCC patients treated with sorafenib ( 43 ). Moreover, GRP78 is linked with activation of the Wnt/catenin pathway in HCC ( 44 ).…”

Section: Er Stress and Immune Suppression In Hccmentioning

confidence: 99%

CCL23 in Balancing the Act of Endoplasmic Reticulum Stress and Antitumor Immunity in Hepatocellular Carcinoma

Karan

2021

Front. Oncol.

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Endoplasmic reticulum (ER) stress is a cellular process in response to stress stimuli in protecting functional activities. However, sustained hyperactive ER stress influences tumor growth and development. Hepatocytes are enriched with ER and highly susceptible to ER perturbations and stress, which contribute to immunosuppression and the development of aggressive and drug-resistant hepatocellular carcinoma (HCC). ER stress-induced inflammation and tumor-derived chemokines influence the immune cell composition at the tumor site. Consequently, a decrease in the CCL23 chemokine in hepatic tumors is associated with poor survival of HCC patients and could be a mechanism hepatic tumor cells use to evade the immune system. This article describes the prospective role of CCL23 in alleviating ER stress and its impact on the HCC tumor microenvironment in promoting antitumor immunity. Moreover, approaches to reactivate CCL23 combined with immune checkpoint blockade or chemotherapy drugs may provide novel opportunities to target hepatocellular carcinoma.

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“…Of note, there were also no small deletions of the HMGA1 and HMGA2 loci indicating rearrangements of these genes or chromosomal bands 6p21 or 12q14-15, respectively, as described in other biphasic breast tumors [ 19 – 24 ].…”

Section: Discussionmentioning

confidence: 64%

Gross genetic alterations and genetic heterogeneity in a periductal stromal tumor of the breast

2020

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Background Periductal stromal tumors of the breast are exceedingly rare biphasic breast tumors with close morphological relationship to phyllodes tumors. So far, results of genetic analyses on these tumors have not been reported. Case presentation A 50 year old female patient was admitted to the hospital because of a palpable lump in her right breast with a diameter of approximately 5–6 cm which was surgically removed by lumpectomy. Histologic examination revealed a biphasic breast tumor classified as periductal stromal tumor. Array analysis showed a pseudotetraploid tumor with a copy number of 4 for most of the chromosomes. In addition, further changes of chromosomes 1, 5, and 6 were noted but there were no mutations of MED12 as those frequently seen in fibroadenomas or phyllodes tumors. Conclusions The genetic alterations observed indicate karyotypic evolution leading to marked heterogeneity which fits with the tumor´s histologic and cytologic appearance as well as with its malignant behavior. Because of the absence of genetic similarities with phyllodes tumors, the case does not offer evidence for a common entity but rather suggests the existence of two independent entities.

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Proteomic Profile of Sorafenib Resistance in Hepatocellular Carcinoma; GRP78 Expression Is Associated With Inferior Response to Sorafenib

Cited by 15 publications

References 29 publications

Omega-3 Fatty Acid-Enriched Fish Oil and Selenium Combination Modulates Endoplasmic Reticulum Stress Response Elements and Reverses Acquired Gefitinib Resistance in HCC827 Lung Adenocarcinoma Cells

Omega-3 Fatty Acid-Enriched Fish Oil and Selenium Combination Modulates Endoplasmic Reticulum Stress Response Elements and Reverses Acquired Gefitinib Resistance in HCC827 Lung Adenocarcinoma Cells

CCL23 in Balancing the Act of Endoplasmic Reticulum Stress and Antitumor Immunity in Hepatocellular Carcinoma

Gross genetic alterations and genetic heterogeneity in a periductal stromal tumor of the breast

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