Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

Liu, Chen-Chi; Li, Hsin-Hsien; Lin, Jiun-Han; Chiang, Ming-Chen; Hsu, Tien‐Wei; Li, Anna Fen–Yau; Yen, David Hung-Tsang; Hsu, Han‐Shui; Hung, Shih‐Chieh

doi:10.3390/biom12010048

Cited by 20 publications

(13 citation statements)

References 32 publications

(40 reference statements)

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“…In this study, we revealed the functional importance of Hspb1 in the proliferation of Tsc2-deficient cells. The mechanistic effect of Hspb1 has been implicated in the regulation of ferroptosis, a mechanism of cell death that is associated with iron metabolism (38,39). In Hspb1-suppressed cells, it is possible that a proliferation suppressive mechanism related to ferroptosis might be induced.…”

Section: Discussionmentioning

confidence: 99%

Induction by rapamycin and proliferation‑promoting activity of Hspb1 in a Tsc2‑deficient cell line

et al. 2023

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Tuberous sclerosis complex (TSC) is an intractable inherited disease caused by a germline mutation in either the TSC complex subunit 1 (TSC1) or TSC2 tumor suppressor genes. Recent progress in the treatment of TSC with rapamycin has provided benefits to patients with TSC. However, the complete elimination of tumors is difficult to achieve as regrowth often occurs after a drug is suspended; thus, more efficient medication and novel therapeutic targets are required. To overcome tumor remnants in the treatment of TSC, the present study investigated rapamycin-responsive signaling pathways in Tsc2-deficient tumor cells, focusing on heat shock protein-related pathways. The expression levels of heat shock protein family B (small) member 1 (Hspb1; also known as HSP25/27) were increased by rapamycin treatment. The phosphorylation of Hspb1 was also increased. The knockdown of Hspb1 suppressed cell proliferation in the absence of rapamycin, and the overexpression of Hspb1 enhanced cell proliferation both in the presence and absence of rapamycin. Pathways associated with Hspb1 may present target candidates for treatment of TSC.

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Section: Discussionmentioning

confidence: 99%

Induction by rapamycin and proliferation‑promoting activity of Hspb1 in a Tsc2‑deficient cell line

et al. 2023

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“…Some compounds have been identified and validated as SLC7A11 inhibitors, including but not limited to erastin, sulfasalazine, sorafenib, imidazole ketone erastin (IKE) and piperazine erastin (PE) [192,196,209]. For EC, as mentioned above, a recent study found that damage from increased lipid peroxidation can be avoided by upregulating GPX4 and SLC7A11, which rescues ESCC cells from ferroptosis, indicating that targeting SLC7A11 to block this intrinsic protective mechanism against ferroptosis has great potential in the treatment of EC [200]. Undoubtedly, SLC7A11 is a promising target in EC therapy.…”

Section: Targeting Slc7a11mentioning

confidence: 98%

Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics

Zhang¹,

Zhang²,

Luan³

et al. 2023

Int. J. Biol. Sci.

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Esophageal cancer (EC) is the sixth most common and the seventh most deadly malignancy of the digestive tract, representing a major global health challenge. Despite the availability of multimodal therapeutic strategies, the existing EC treatments continue to yield unsatisfactory results due to their limited efficacy and severe side effects. Recently, knowledge of the subroutines and molecular mechanisms of regulated cell death (RCD) has progressed rapidly, enhancing the understanding of key pathways related to the occurrence, progression, and treatment of many types of tumors, including EC. In this context, the use of small-molecule compounds to target such RCD subroutines has emerged as a promising therapeutic strategy for patients with EC. Thus, in this review, we firstly discussed the risk factors and prevention of EC. We then outlined the established treatment regimens for patients with EC. Furthermore, we not only briefly summarized the mechanisms of five best studied subroutines of RCD related to EC, including apoptosis, ferroptosis, pyroptosis, necroptosis and autophagy, but also outlined the recent advances in the development of small-molecule compounds and long non-coding RNA (lncRNA) targeting the abovementioned RCD subroutines, which may serve as a new therapeutic strategy for patients with EC in the future.

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“…compared with normal tissues, GPX4 expression levels are significantly elevated in a variety of tumor tissues, such as triple-negative breast (80), gastric (81) and esophageal (82) cancer, leading to the hypothesis that GPX4 may be an oncogene. It has been shown to be a key regulator of ferroptosis; the overexpression or knockdown of GPX4 can affect the cell lethality of 12 ferroptosis inducers (83).…”

Section: Regulation Of Ferroptosis Through the Gpx4 Pathwaymentioning

confidence: 99%

Advances in the study of regulators of ferroptosis in head and neck squamous cell carcinoma (Review)

et al. 2023

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Head and neck squamous cell carcinoma (HNScc), a common malignancy of the head and neck, is associated with a rapid progression, a high mortality rate and unsatisfactory curative effects. The treatment efficacy is unsatisfactory due to chemotherapeutic drug resistance, the lack of ideal therapeutic agents, as well as the absence of clinical prognostic models. Thus, the identification of novel potential therapeutic targets for its diagnosis and treatment is vital. Ferroptosis is an iron-dependent regulatory cell death mode different from traditional cell death modes, such as apoptosis and autophagy, and has notable therapeutic potential in cancer treatment. The study of ferroptosis in HNScc is expected to solve this bottleneck problem. In the present review, the findings, characteristics and regulatory mechanisms of ferroptosis are summarized, with emphasis on the factors and drugs that regulate ferroptosis in HNScc, in order to provide theoretical basis for the targeted therapy of ferroptosis in HNScc. Contents1. Introduction 2. data collection methods 3. The discovery and characteristics of ferroptosis 4. Regulatory mechanisms of ferroptosis 5. Ferroptosis regulators in head and neck squamous cell carcinoma 6. Therapeutic modalities regulating ferroptosis in head and neck squamous carcinoma 7. conclusions and future perspectives

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Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

Cited by 20 publications

References 32 publications

Induction by rapamycin and proliferation‑promoting activity of Hspb1 in a Tsc2‑deficient cell line

Induction by rapamycin and proliferation‑promoting activity of Hspb1 in a Tsc2‑deficient cell line

Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics

Advances in the study of regulators of ferroptosis in head and neck squamous cell carcinoma (Review)

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