Role of STAT3 in Colorectal Cancer Development

Lakkim, Vajravathi; Reddy, Madhava C.; Prasad, Durbaka V. R.; Lomada, Dakshayani

doi:10.1007/978-981-10-6728-0_19

Cited by 6 publications

(5 citation statements)

References 143 publications

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“…Furthermore, Hsp110 is involved in STAT3 phosphorylation in the cytosol, thereby promoting cell proliferation ([ 72 ], Figure 3 ). STAT3 is constitutively activated in several cancers and is thought to play a critical role in tumor growth and metastasis [ 80 , 81 , 82 , 83 ]. STAT3 also regulates several signaling pathways such as cellular proliferation, invasion and angiogenesis, which are all critical for metastasis [ 84 , 85 ].…”

Section: Hsp110 Roles In Cancer Pathogenesismentioning

confidence: 99%

The Role of Non-Canonical Hsp70s (Hsp110/Grp170) in Cancer

Chakafana

Shonhai

2021

Cells

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Although cancers account for over 16% of all global deaths annually, at present, no reliable therapies exist for most types of the disease. As protein folding facilitators, heat shock proteins (Hsps) play an important role in cancer development. Not surprisingly, Hsps are among leading anticancer drug targets. Generally, Hsp70s are divided into two main subtypes: canonical Hsp70 (Escherichia coli Hsp70/DnaK homologues) and the non-canonical (Hsp110 and Grp170) members. These two main Hsp70 groups are delineated from each other by distinct structural and functional specifications. Non-canonical Hsp70s are considered as holdase chaperones, while canonical Hsp70s are refoldases. This unique characteristic feature is mirrored by the distinct structural features of these two groups of chaperones. Hsp110/Grp170 members are larger as they possess an extended acidic insertion in their substrate binding domains. While the role of canonical Hsp70s in cancer has received a fair share of attention, the roles of non-canonical Hsp70s in cancer development has received less attention in comparison. In the current review, we discuss the structure-function features of non-canonical Hsp70s members and how these features impact their role in cancer development. We further mapped out their interactome and discussed the prospects of targeting these proteins in cancer therapy.

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Section: Hsp110 Roles In Cancer Pathogenesismentioning

confidence: 99%

The Role of Non-Canonical Hsp70s (Hsp110/Grp170) in Cancer

Chakafana

Shonhai

2021

Cells

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“…When focusing on colorectal cancer, 307 proteins were altered between healthy, early, and late stages. These include three with a documented role in colorectal cancer development: STAT3, 58 TAGL, 59 and CD47. 60 In addition, gene ontology enrichments based on identified candidates showed a response to leptin and the regulation of proteolysis increased in cancer.…”

Section: Discussionmentioning

confidence: 99%

Biomarker Candidates for Tumors Identified from Deep-Profiled Plasma Stem Predominantly from the Low Abundant Area

et al. 2022

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The plasma proteome has the potential to enable a holistic analysis of the health state of an individual. However, plasma biomarker discovery is difficult due to its high dynamic range and variability. Here, we present a novel automated analytical approach for deep plasma profiling and applied it to a 180-sample cohort of human plasma from lung, breast, colorectal, pancreatic, and prostate cancers. Using a controlled quantitative experiment, we demonstrate a 257% increase in protein identification and a 263% increase in significantly differentially abundant proteins over neat plasma. In the cohort, we identified 2732 proteins. Using machine learning, we discovered biomarker candidates such as STAT3 in colorectal cancer and developed models that classify the diseased state. For pancreatic cancer, a separation by stage was achieved. Importantly, biomarker candidates came predominantly from the low abundance region, demonstrating the necessity to deeply profile because they would have been missed by shallow profiling.

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“…STAT3 mediates differentiation of preadipocytes to mature adipocytes, augmenting lipid accumulation, whereas STAT3 inhibition stops preadipocyte differentiation( 24 ). Additionally, STAT3 is a transcription factor for oncogenic signalling in CRC that is associated with poor prognosis and lymph node involvement( 19 , 22 ) and has been linked to adverse inflammatory response and poor survival in CRC patients( 20 ). STAT3 transduces signals from extracellular stimuli to several interferons (IFN- α, -β, and - γ) and cytokines (gp130, IL-2, -6, -12, -15, -21 and -23) and thereby directs cell transformation and tumourigenesis( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa

et al. 2021

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Background/Objectives Obesity increases colorectal cancer (CRC) risk. However, the effects of weight loss on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We examined the effects of obesity and weight loss following Roux-en-Y gastric bypass (RYGB) on microRNA expression in the human rectal mucosa. Subjects/Methods We collected rectal mucosal biopsies from obese patients (n = 22) listed for RYGB and age- and sex-matched healthy non-obese Controls (n = 20), at baseline and six months post-surgery. We quantified microRNA expression in rectal mucosal biopsies using Next Generation Sequencing and bioinformatics analysis to investigate the likely functional consequences of these epigenetic changes. Results Compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). At six-months post-RYGB, when mean body mass had fallen by 27 kg, 60 microRNAs were differentially expressed, compared with baseline (p < 0.05). The expression of 36 microRNAs differed significantly between both i) obese and non-obese individuals and ii) obese individuals pre- and post-RYGB. Quantitative polymerase chain reaction (qPCR) demonstrated that expression of miR-31 and miR-215 was significantly (p < 0.05) higher, 143-fold and 15-fold respectively, in obese than in non-obese individuals. Weight loss, following RYGB, reduced expression of miR-31 and miR-215 to levels comparable with Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer. Conclusion Our findings show, for the first time, that obesity is associated with dysregulated microRNA expression in the human rectal mucosa. Further, surgically-induced weight loss may normalise microRNA expression in this tissue.

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Role of STAT3 in Colorectal Cancer Development

Cited by 6 publications

References 143 publications

The Role of Non-Canonical Hsp70s (Hsp110/Grp170) in Cancer

The Role of Non-Canonical Hsp70s (Hsp110/Grp170) in Cancer

Biomarker Candidates for Tumors Identified from Deep-Profiled Plasma Stem Predominantly from the Low Abundant Area

Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa

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