Skip to Content
Merck

c-Src drives intestinal regeneration and transformation.

The EMBO journal (2014-05-03)
Julia B Cordero, Rachel A Ridgway, Nicola Valeri, Colin Nixon, Margaret C Frame, William J Muller, Marcos Vidal, Owen J Sansom
ABSTRACT

The non-receptor tyrosine kinase c-Src, hereafter referred to as Src, is overexpressed or activated in multiple human malignancies. There has been much speculation about the functional role of Src in colorectal cancer (CRC), with Src amplification and potential activating mutations in up to 20% of the human tumours, although this has never been addressed due to multiple redundant family members. Here, we have used the adult Drosophila and mouse intestinal epithelium as paradigms to define a role for Src during tissue homeostasis, damage-induced regeneration and hyperplasia. Through genetic gain and loss of function experiments, we demonstrate that Src is necessary and sufficient to drive intestinal stem cell (ISC) proliferation during tissue self-renewal, regeneration and tumourigenesis. Surprisingly, Src plays a non-redundant role in the mouse intestine, which cannot be substituted by the other family kinases Fyn and Yes. Mechanistically, we show that Src drives ISC proliferation through upregulation of EGFR and activation of Ras/MAPK and Stat3 signalling. Therefore, we demonstrate a novel essential role for Src in intestinal stem/progenitor cell proliferation and tumourigenesis initiation in vivo.

MATERIALS
Product Number
Brand
Product Description

Supelco
Sucrose, Pharmaceutical Secondary Standard; Certified Reference Material
SKU
Pack Size
Availability
Price
Quantity
USP
Sucrose, United States Pharmacopeia (USP) Reference Standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, puriss., meets analytical specification of Ph. Eur., BP, NF
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, BioUltra, for molecular biology, ≥99.5% (HPLC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, ACS reagent
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, meets USP testing specifications
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, ≥99.5% (GC), Grade II, suitable for plant cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, Grade I, ≥99% (GC), suitable for plant cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, ≥99.5% (GC), BioReagent, suitable for cell culture, suitable for insect cell culture
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, ≥99.5% (GC), BioXtra
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, ≥99.5% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, ≥99.5% (GC)
SKU
Pack Size
Availability
Price
Quantity
Supelco
Sucrose, analytical standard, for enzymatic assay kit SCA20
SKU
Pack Size
Availability
Price
Quantity
Sucrose, European Pharmacopoeia (EP) Reference Standard
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sucrose, for molecular biology, ≥99.5% (GC)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
DAPI, for nucleic acid staining
SKU
Pack Size
Availability
Price
Quantity
Millipore
Sucrose, suitable for microbiology, ACS reagent, ≥99.0%
SKU
Pack Size
Availability
Price
Quantity