Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis

Bian, Benjamin; Mongrain, Sébastien; Cagnol, Sébastien; Langlois, Marie‐Josée; Boulanger, Jim; Bernatchez, Gérald; Carrier, Julie; Boudreau, François; Rivard, Nathalie

doi:10.1002/mc.22312

Cited by 127 publications

(93 citation statements)

References 47 publications

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“…Fifty‐seven specimens of colon tumor and paired normal tissue (at least 10 cm from the tumor) were obtained from patients who underwent surgical resection and were processed as previously described (31). Patients did not receive neoadjuvant therapy.…”

Section: Methodsmentioning

confidence: 99%

Epithelial Src homology region 2 domain–containing phosphatase‐1 restrains intestinal growth, secretory cell differentiation, and tumorigenesis

et al. 2017

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Shp-1 (Src homology region 2 domain-containing protein tyrosine phosphatase-1) is a phosphatase that is highly expressed in hematopoietic and epithelial cells. Whereas its function is largely characterized in hematopoietic cells, its role in epithelial cells, such as intestinal epithelial cells (IECs), is not well known. Here, we generated mice with an IEC-specific knockout of Shp-1 (Src homology region 2 domain-containing phosphatase-1; Shp-1 IEC-KO ). We showed that the loss of epithelial Shp-1 leads to an intestinalomegaly that is associated with an increase in epithelial cell proliferation and size. Histologic analysis demonstrates significant perturbation of the crypt-villus architecture with an apparent increase in the number of goblet and Paneth cells and increased expression of their respective markers {Muc2 (mucin 2), aDef, and Sox9 [SRY (sex determining region Y)-box 9]}. Expansion of intermediate cells-common progenitors of goblet and Paneth cell lineages-is also observed in Shp-1 IEC-KO mice. Although sustained activation of Wnt/b-catenin and PI3K/Akt/mammalian target of rapamycin signaling is observed, Shp-1 IEC-KO mice fail to develop any intestinal tumors after 15 mo; however, the loss of Shp-1 in IECs markedly enhances tumor load Apc Min/+ mice. These findings show a novel role for Shp-1 in the regulation of IEC growth and secretory lineage allocation, possibly via modulation of PI3K/Akt-dependent signaling pathways. Finally, Shp-1 does not function as a classic tumor suppressor gene in the intestinal

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Section: Methodsmentioning

confidence: 99%

Epithelial Src homology region 2 domain–containing phosphatase‐1 restrains intestinal growth, secretory cell differentiation, and tumorigenesis

et al. 2017

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“…[76][77][78][79] CTSB is able to recognize and cleave peptides with a specific sequence. This linker was targeted by the endopeptidase CTSB in order to achieve controllable and specific cleavage due to its overexpression in various cancers.…”

Section: Doi: 101002/adtp201800110mentioning

confidence: 99%

Nanodiamond‐Based Platform for Intracellular‐Specific Delivery of Therapeutic Peptides against Hepatocellular Carcinoma

Wang

Toh

et al. 2018

Advanced Therapeutics

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Therapeutic peptides are attractive as a treatment modality due to their high selectivity and relative safety and tolerability. Delivery of therapeutic peptides to target cells continues to pose a challenge, particularly when these peptides target intracellular proteins. In this study, the use of nanodiamonds (NDs) as a platform for enhanced intracellular delivery of therapeutic peptides is investigated. SALL4 is found to contribute to tumor progression in many types of cancers, including hepatocellular carcinoma (HCC). Therapeutic peptides specifically targeting SALL4 demonstrate an effective, but limited, inhibitory effect on SALL4-driven HCC tumor cell growth. Nanodiamond-based delivery of SALL4-inhibitory peptides is found to improve peptide stability and cellular peptide retention. Stimuli-responsive release of SALL4-inhibitory peptide from nanodiamonds ensures intracellular-specific delivery of functional SALL4-inhibitory peptides. The observed enhanced peptide stability and intracellular-specific delivery of SALL4-inhibitory peptides by nanodiamonds result in improved therapeutic efficacy by ND-peptide complexes against SALL4-driven HCC. As such, nanodiamonds serve as a promising platform for stimuli-responsive intracellular-specific delivery of therapeutic peptides.Therapeutic peptides have been applied toward treating a wide range of diseases. [1][2][3][4][5][6] Various therapeutic applications of peptides include serving as hormones, inhibitors, drug carriers, and even anticancer agents. [1][2][3][4][7][8][9][10][11][12][13] However, hurdles toward clinical implementation for some peptides exist due to the intrinsic

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“…Other organs which also CRC metastasize are the lung and bone. [9,10] There are several examinations such as; blood testing, immunochemical/molecular testing, and colonoscopy-based screening which are used for screening in developed countries as a preventive measure for the detection of CRC in its early stages. Colorectal cancer diagnosed in early stage is known that 10% to 30% still relapses with metastases within two years of surgical treatment.…”

Section: Ivyspringmentioning

confidence: 99%

Colorectal Cancer from Molecular Pathways to Gene Therapy

Kosmıdis¹,

Efthimidis²,

Baka³

et al. 2017

Oncomedicine

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Nowadays colorectal cancer is still considered the third most common cancer in the world. The tumorigenesis mechanisms of colorectal cancer have been widely studied at a molecular level. It has been observed that morbidity and mortality caused by colorectal cancer impacts on the global economy. This occurs through the loss of productivity and the burden on the healthcare system. Therefore an effort is made by several researchers to expend considerably their resources to develop treatments and preventative strategies to reduce the incidence of colorectal cancer. A Large-scale sequencing of genome, proteome, microbiome, and transcriptome analyses of colorectal cancer tissue has allowed researchers to better understand colorectal cancer subtypes. Until now the following parameters have been identified with the etiology of colorectal cancer genetic mutations, inflammatory processes, diet, and the gut microbes. In the current review we will present the molecular pathways of CRC and discuss novel gene therapy approaches.

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Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis

Cited by 127 publications

References 47 publications

Epithelial Src homology region 2 domain–containing phosphatase‐1 restrains intestinal growth, secretory cell differentiation, and tumorigenesis

Epithelial Src homology region 2 domain–containing phosphatase‐1 restrains intestinal growth, secretory cell differentiation, and tumorigenesis

Nanodiamond‐Based Platform for Intracellular‐Specific Delivery of Therapeutic Peptides against Hepatocellular Carcinoma

Colorectal Cancer from Molecular Pathways to Gene Therapy

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