Most computational methods are developed to analyze microsc

We showed greater phosphorylation of IGF 1R in BCSCs

than in non BCSCs and preferential sensitivity of BCSCs

to PPP, a specific inhibitor of the IGF 1R, leading to

reduced phosphorylation of AktSer473 and decreased ALDH

ARQ 197

905854-02-6 BCSC populations. In human

malignancies, increased circulating IGF 1 was associated

with a greater risk of several cancers, including breast

cancer, A crosstalk between IGF 1R and the Wnt pathway

has been reported in colon cancer, oligo dendroglial

cells, and chondrocytes, The inter action of these two

pathways in breast cancer is intriguing and awaits

further investigation.<br><br> Recently, two reports

demonstrated the essential role of IGF IGF 1R signaling

in the maintenance of leukemia initiating cells in T

cell acute lymphoblastic leukemia or in the

transformation of hematopoietic progenitor cells in the

mouse model of acute myelogenous leukemia,

AZD0530

Bcr-Abl 阻害剤 The IGF 1R expression of leukemia

initiating cells in T cell acute lymphoblastic leukemia

was maintained by Notch signaling, which also

contributed to the mainte nance of BCSCs, Whether the

Notch pathway is involved in the IGF 1R signaling in

BCSCs remains to be investigated. In solid tumors,

chemoresistant colorec tal cells displayed a CSC

phenotype and became more sensitive to IGF 1R

inhibition, In hepatocellular carcinoma, the IGF 2 IGF

1R signal was shown to be involved in Nanog mediated

self renewal of hepatic CSCs, These reports also support

the importance of IGF 1R in CSC biology.<br><br> In

breast cancer, activation of the IGF 1R could result in

stimulation of proliferation and metastasis through

activation of insulin receptor substrate 1 and insulin

receptor substrate 2, Furthermore, it has been reported

that IGF 1R expres sion was positively correlated with a

shorter disease free survival in triple negative breast

cancer, the particu lar subtype with the highest rate

オ

ーダー Alvocidib of recurrence and higher

percentage of BCSCs than other breast cancer subtypes,

In a recent report by Jones and collea gues, recurrence

of breast cancer was observed in 16% of inducible IGF 1R

transgenic mice upon the disconti nuation of doxycycline

and the recurrence involved IGF 1R reactivation and IGF

1R independent mechanisms, Although the IGF 1R

independent tumors dis played EMT phenotypes, their

metastatic potential was much lower than tumors with IGF

1R reactivation, Moreover, induction of EMT in

immortalized human mammary epithelial cells by

overexpressing EMT related transcriptional factors,

twist or snail, or treatment with transforming growth

factor b1 generated CD44 BCSCs, Recently, Lorenzatti and

colleagues found that CCN6, a tumor inhibitory protein,

could suppress the expression of EMT transcriptional

factor ZEB1 in breast cancer cells through attenuation

of IGF 1R signaling, Along this line, we also showed

that inhibition of IGF 1R signaling suppressed the cell

migration ability of CD44 BCSCs through induction of E

cadherin, the adhesion molecule that blocks the EMT

process, as well as suppression of other mesenchymal

markers, More importantly, IGF 1R could serve as a novel

marker for a particular population of cancer cells with

stem progenitor features within breast cancer since IGF

1R high expressing human breast can cer cells displayed

the capacity for mammosphere for mation in vitro and

tumorigenicity in vivo.<br><br>