Search for directed genic interactions:  

MTOR SLC22A3 (1 - 2 of 2)
PMID: 21367918
Albumin-induced epithelial-mesenchymal transition and ER stress are regulated through a common ROS-c-Src kinase-mTOR pathway: effect of imatinib mesylate.
... and mTOR inhibitor... suppressed the... -induced EMT and ...   (details)

MTOR SLC22A3

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 21367918

Albumin-induced epithelial-mesenchymal transition and ER stress are regulated through a common ROS-c-Src kinase-mTOR pathway: effect of imatinib mesylate.
Source

American journal of physiology. Renal physiology (May 2011)

Abstract

Albumin-induced epithelial-mesenchymal transition and ER stress are regulated through a common ROS-c-Src kinase-mTOR pathway: effect of imatinib mesylate. The epithelial-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress induced by urinary protein, particularly albumin, play an important role in tubulointerstitial injury. However, signaling pathways regulating both albumin-induced EMT and ER stress are not precisely known. We postulated that reactive oxygen species (ROS), c-Src kinase, and mammalian target of rapamysin (mTOR) would act as upstream signaling molecules. We further examined the effect of imatinib mesylate on these processes. All experiments were performed using HK-2 cells, a human proximal tubular cell line. Protein and mRNA expression were measured by Western blot analysis and real-time PCR, respectively. Exposure of tubular cells to albumin (5 mg/ml) for up to 5 days induced EMT in a time-dependent manner, as shown by conversion to the spindle-like morphology, loss of E-cadherin protein, and upregulation of a-smooth muscle actin mRNA and protein. Albumin also induced ER stress as evidenced by phosphorylation of eukaryotic translation initiation factor-2a and increased expression of GRP78 mRNA and protein. Albumin induced ROS, c-Src kinase, and mTOR as well. Antioxidants, c-Src kinase inhibitor (PP2), and mTOR inhibitor (rapamycin) suppressed the albumin-induced EMT and ER stress. Antioxidants and PP2 inhibited the albumin-induced c-Src kinase and mTOR, respectively. Imatinib suppressed the albumin-induced EMT and ER stress via inhibition of ROS and c-Src kinase. Imatinib also inhibited the albumin-induced mRNA expression of MCP-1, VCAM-1, transforming growth factor (TGF) -ß1, and collagen I (a1). In conclusion, the ROS-c-Src kinase-mTOR pathway played a central role in the signaling pathway that linked albumin to EMT and ER stress. Imatinib might be beneficial in attenuating the albumin-induced tubular injury.

PMID: 21430067
mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways.
... and mTORC2 regulate EMT, ...   (details)

MTOR SLC22A3

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTORC2   (MAPKAP1   MLST8   RICTOR   PRR5   MTOR )

PMID: 21430067

mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways.
Source

Cancer research (5/1/2011)

Abstract

mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Activation of phosphoinositide 3-kinase (PI3K) /Akt signaling is associated with growth and progression of colorectal cancer (CRC). We have previously shown that the mTOR kinase, a downstream effector of PI3K/Akt signaling, regulates tumorigenesis of CRC. However, the contribution of mTOR and its interaction partners toward regulating CRC progression and metastasis remains poorly understood. We found that increased expression of mTOR, Raptor, and Rictor mRNA was noted with advanced stages of CRC, suggesting that mTOR signaling may be associated with CRC progression and metastasis. mTOR, Raptor, and Rictor protein levels were also significantly elevated in primary CRCs (stage IV) and their matched distant metastases compared with normal colon. Inhibition of mTOR signaling, using rapamycin or stable inhibition of mTORC1 (Raptor) and mTORC2 (Rictor), attenuated migration and invasion of CRCs. Furthermore, knockdown of mTORC1 and mTORC2 induced a mesenchymal-epithelial transition (MET) and enhanced chemosensitivity of CRCs to oxaliplatin. We observed increased cell-cell contact and decreased actin cytoskeletal remodeling concomitant with decreased activation of the small GTPases, RhoA and Rac1, upon inhibition of both mTORC1 and mTORC2. Finally, establishment of CRC metastasis in vivo was completely abolished with targeted inhibition of mTORC1 and mTORC2 irrespective of the site of colonization. Our findings support a role for elevated mTORC1 and mTORC2 activity in regulating epithelial-mesenchymal transition (EMT), motility, and metastasis of CRCs via RhoA and Rac1 signaling. These findings provide the rationale for including mTOR kinase inhibitors, which inhibit both mTORC1 and mTORC2, as part of the therapeutic regimen for CRC patients.