The role of heat shock proteins in metastatic colorectal cancer: A review

Javid, Hossein; Hashemian, Pedram; Yazdani, Shaghayegh; Mashhad, Alireza Sharbaf; Karimi‐Shahri, Mehdi

doi:10.1002/jcb.30326

Cited by 18 publications

(18 citation statements)

References 282 publications

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“…Overexpression of mortalin correlates with diminished patient survival in several forms of cancer, including early-stage non-small cell lung cancer ( Sun et al, 2017 ), breast cancer ( Zhang et al, 2021 ), hepatocellular carcinoma ( Cheng et al, 2019 ), ovarian and cervical cancers ( Putri et al, 2019 ; Xu et al, 2019 ), gastric cancer ( Dai et al, 2021 ), and CRC ( Rozenberg et al, 2013 ; Javid et al, 2022 ). In the context of CRC, overexpressed mortalin was observed in adenoma and colorectal adenocarcinomas ( Dundas et al, 2005 ).…”

Section: Mortalin and Tumorigenic Pathwaysmentioning

confidence: 99%

“…However, patterns of HSP expression are selectively determined by the stages of cancer as well as tissue types. Some examples are the biological impacts and prognostic values of HSPs (HSP27, HSP60, and HSP70) in prostate, breast, and colorectal cancers in both early and advanced cancers ( Glaessgen et al, 2008 ; Javid et al, 2022 ; Sun et al, 2022 ; Tsai et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities

Esfahanian

Knoblich

Bowman

et al. 2023

Front. Cell Dev. Biol.

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Mortalin (GRP75, HSPA9A), a heat shock protein (HSP), regulates a wide range of cellular processes, including cell survival, growth, and metabolism. The regulatory functions of mortalin are mediated through a diverse set of protein partners associated with different cellular compartments, which allows mortalin to perform critical functions under physiological conditions, including mitochondrial protein quality control. However, alteration of mortalin’s activities, its abnormal subcellular compartmentalization, and its protein partners turn mortalin into a disease-driving protein in different pathological conditions, including cancers. Here, mortalin’s contributions to tumorigenic pathways are explained. Pathology information based on mortalin’s RNA expression extracted from The Cancer Genome Atlas (TCGA) transcriptomic database indicates that mortalin has an independent prognostic value in common tumors, including lung, breast, and colorectal cancer (CRC). Subsequently, the binding partners of mortalin reported in different cellular models, from yeast to mammalian cells, and its regulation by post-translational modifications are discussed. Finally, we focus on colorectal cancer and discuss how mortalin and its tumorigenic downstream protein targets are regulated by a ubiquitin-like protein through the 26S proteasomal degradation machinery. A broader understanding of the function of mortalin and its positive and negative regulation in the formation and progression of human diseases, particularly cancer, is essential for developing new strategies to treat a diverse set of human diseases critically associated with dysregulated mortalin.

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Section: Mortalin and Tumorigenic Pathwaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities

Esfahanian

Knoblich

Bowman

et al. 2023

Front. Cell Dev. Biol.

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“…Additionally, Hsp40 facilitates the binding of Hsp70 to the Hsp90-Hop (heat shock organizing protein) complex for further control of the protein folding [ 22 , 23 , 24 ]. Taking into consideration the protective role of HSPs, the overexpression of chaperones was reported in various types of solid and hematological malignancies [ 25 , 26 , 27 , 28 , 29 ]. High expression of HSPs also correlated to the chemo- and radioresistance of tumors indicated the possibility of employing these proteins as prognostic and/or diagnostic markers [ 26 , 30 , 31 , 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.

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“…Members of the Hsp90 family have a molecular weight range of 81–99 kDa, and are found in the cytosol, mitochondria, endoplasmic reticulum and nucleus of the cells and have multiple functions, including the autoregulation of the heat shock response, the folding of new proteins and influencing the cell cycle and cell proliferation [ 19 ]. The Hsp 90 family includes the constitutively expressed Hsp 90β and its stress-induced isoform, Hsp 90α, along with other members, TNF-receptor-associated protein1 (TRAP1) and glucose-regulated protein 94 (GRP94) [ 19 ]. Increasing evidence has demonstrated that Hsps, including small Hsp-s, play important roles in different types of tumors [ 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…Increasing evidence has demonstrated that Hsps, including small Hsp-s, play important roles in different types of tumors [ 20 , 21 , 22 , 23 ]. Hsp 90 has been shown to influence multiple signal pathways associated with cell cycle arrest and apoptosis, the regulation of invasion and metastasis and the sensitization of drug resistance [ 19 , 24 , 25 , 26 ]. Hsp 90 has been reported to be upregulated in colorectal cancer tissue compared to healthy colon tissues, which has led to investigations regarding the use of Hsp 90 inhibitors as potential therapeutic agents in colorectal cancer [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer

et al. 2023

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Background: Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses, and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins, including growth-hormone-releasing hormone receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL, in specimens of locally advanced rectal cancer patients, as well as the time to metastasis and 10-year overall survival (OS) rates. We also investigated whether these outcome measures were associated with the presence of other clinical parameters. Methods: In total, 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for the proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan–Meier curves were used to show the relationships between the intensity of expression of biomarkers, clinical parameters, the time to metastasis and the 10-year OS rate. Results: High levels of p-Akt, GHRH-R and Hsp90 were associated with a significantly decreased 10-year OS rate (p = 0.001, p = 0.000, p = 0.004, respectively) and high expression levels of p-Akt and GHRH-R were correlated with a significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both a significantly longer time to metastasis and an improved 10-year OS rate. Conclusions: Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of the 10-year OS rate in locally advanced rectal cancer patients. The GHRH-R and Hsp90 expression levels were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for the anticancer treatment of advanced rectal cancer.

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The role of heat shock proteins in metastatic colorectal cancer: A review

Cited by 18 publications

References 282 publications

Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities

Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer

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