TGFβ-1 increases cell proliferation, wound healing and induces changes to membrane proteome in colorectal cancer cells with varying integrin β6 expression — ASN Events
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TGFβ-1 increases cell proliferation, wound healing and induces changes to membrane proteome in colorectal cancer cells with varying integrin β6 expression (#103)

Harish R Cheruku 1 , David I Cantor 1 , Abidali Mohamedali 2 , Sock-Hwee Tan 2 , Seong B Ahn 1 , Edouard C Nice 3 , Mark S Baker 1
  1. Australian School of Advanced Medicine, Macquarie University, North Ryde, NSW, Australia
  2. Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW, Australia
  3. Monash University, Clayton, Victoria, Australia

It is well understood that Transforming Growth Factor-β (TGFβ) signalling is a potent regulator of cell growth, differentiation, migration and tumour suppression. However, during colorectal cancer (CRC) and other cancers TGFβ mRNA and protein show marked increases are associated with tumour growth. The involvement of TGFβ as tumour promoter is poorly understood. We hypothesise that the increased expression of TGFβ can be achieved by high expression levels of integrin αvβ6, which can activate latent-TGFβ and MMP-9 both of which are activators of latent-TGFβ. High expression of integrin αvβ6 has been observed in various cancers including CRC. Cell proliferation and would healing assays showed significant differences when treated with active TGFβ. To gain more in-depth understanding of role of TGFβ, αvβ6 and uPAR in CRC we compared the membrane proteome of TGFβ1 (10ng/mL) stimulated SW480 cells with none or overexpressing integrin β6 using iTRAQ. We identified 2666 proteins, out of which 510 proteins were from the plasma membrane. The IPA analysis with significantly altered proteins revealed cellular assembly and organization, cell-to-cell signalling and interaction as the top-ranked altered biological function. Ingenuity pathway analysis also showed RAN and EIF2 signalling were amongst top 5 canonical pathways identified. We identified various proteins including integrins (α3β1, α4β1, α6β1, α5β1, αv), ERK1/2, TGFβ and MAPK1/2 through IPA network analysis. All these molecules have been previously implicated in various cancers including CRC. The results show that TGFβ signalling is enhancing the ability of the cancer cells towards progression and metastasis. Therefore, it is very important to study the TGFβ associated protein-protein interactions during CRC which will serve to identify novel key players for metastasis, and serve as biomarkers and/or drug targets to improve CRC therapy.