Mechanisms of acquired resistance to insulin-like growth factor 1 receptor inhibitor in MCF-7 breast cancer cell line

Ekyalongo, Roudy Chiminch; Mukohara, Toru; Kataoka, Yu; Funakoshi, Yohei; Tomioka, Hideo; Kiyota, Naomi; Fujiwara, Yutaka; Minami, Hironobu

doi:10.1007/s10637-012-9855-1

Cited by 14 publications

(11 citation statements)

References 41 publications

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“…After gaining resistance to the estrogen deprivation, ERα+ cells show upregulation and activation of IGF-I/IGF-IR and PI3K/AKT signaling [44]. Furthermore, IGF-IR inhibitors also gain rapid resistance [45, 46]. It is urgently needed to find other options for targeting IGF-I/IGF-IR in ERα+ and ERα- cells rather than conventional direct therapies.…”

Section: Discussionmentioning

confidence: 99%

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer

et al. 2016

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Breast cancer is the second leading cause of cancer deaths among women. Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system. Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood. We observed that estrogen receptor-α negative (ERα-) breast cancer cells highly express epidermal growth factor receptor (EGFR) as well as insulin-like growth factor-I receptor (IGF-IR). We also observed IGF-IR upregulation in ERα+ breast cancer cells. In addition, we found that higher CNR2 expression correlates with better recurrence free survival in ERα- and ERα+ breast cancer patients. Therefore, we analyzed the role of CNR2 specific agonist (JWH-015) on EGF and/or IGF-I-induced tumorigenic events in ERα- and ERα+ breast cancers. Our studies showed that CNR2 activation inhibited EGF and IGF-I-induced migration and invasion of ERα+ and ERα- breast cancer cells. At the molecular level, JWH-015 inhibited EGFR and IGF-IR activation and their downstream targets STAT3, AKT, ERK, NF-kB and matrix metalloproteinases (MMPs). In vivo studies showed that JWH-015 significantly reduced breast cancer growth in ERα+ and ERα- breast cancer mouse models. Furthermore, we found that the tumors derived from JWH-015-treated mice showed reduced activation of EGFR and IGF-IR and their downstream targets. In conclusion, we show that CNR2 activation suppresses breast cancer through novel mechanisms by inhibiting EGF/EGFR and IGF-I/IGF-IR signaling axes.

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Section: Discussionmentioning

confidence: 99%

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer

et al. 2016

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“…The OSI-906-induced phosphorylation of p70S6K1 and MDM2 was inhibited and thereby cleaved caspase 3 and apoptosis was increased when Pdcd4 was over-expressed in the resistant cells. In addition to CRC cells, the elevation of phospho-p70S6K level was also observed in the IGF-1R inhibitor-resistant breast MCF7 cells (41). These findings collectively suggest that OSI-906 resistance in CRC cells is at least partially contributed by activation of p70S6K1.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF-1R/IR Inhibitor in Colon Carcinoma Cells

Zhang

Wang

Chen

et al. 2015

Molecular Cancer Therapeutics

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Agents targeting insulin-like growth factor 1 receptor (IGF-1R) are being actively examined in clinical trials. Although there has been some initial success of single agent targeting IGF-1R, attempts in later studies failed due to resistance. This study aimed to understand the effects of programmed cell death 4 (Pdcd4) on the chemosensitivity of the IGF-1R inhibitor, OSI-906, in colorectal cancer (CRC) cells and the mechanism underlying this impact. Using OSI-906 resistant and sensitive CRC cells, we found that the Pdcd4 level directly correlates with cell chemosensitivity to OSI-906. In addition, tumors derived from Pdcd4 knockdown cells resist the growth inhibitory effect of OSI-906 in a CRC xenograft mouse model. Moreover, Pdcd4 enhances the antiproliferative effect of OSI-906 in resistant cells through suppression of p70S6K1 activation. Knockdown of p70S6K1, but not p70S6K2, significantly increases the chemosensitivity of OSI-906 in cultured CRC cells. Furthermore, the combination of OSI-906 and PF4708671, a p70S6K1 inhibitor, efficiently suppresses the growth of OSI-906 resistant colon tumor cells in vitro and in vivo. Taken together, activation of p70S6K1 that is inhibited by Pdcd4 is essential for resistance to IGF-1R inhibitor in colon tumor cells, and the combinational treatment of OSI-906 and PF-4708671 results in enhanced antiproliferation effects in CRC cells in vitro and in vivo, providing a novel venue to overcome the resistance to IGF-1R inhibitor in treating colorectal cancer.

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“…152 TYRO3 also regulates the proliferation of MCF-7 breast cancer cells through control of cyclin D1 expression and phosphorylation of ERK1/2 or STAT3. 142,153 These studies reveal that TYRO3 may utilize distinct signaling pathways to transmit its message in different cell types. Further study is warranted to systemically characterize the second messengers directly downstream of TYRO3.…”

Section: Tyro3 Signaling Pathwaysmentioning

confidence: 99%

TYRO3: A potential therapeutic target in cancer

Hsu

Jou

Tsai

2019

Exp Biol Med (Maywood)

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TYRO3 belongs to the TAM (TYRO3, AXL, and MER) receptor family, a unique subfamily of the receptor tyrosine kinases. Members of TAM family share the same ligand, growth arrest-specific 6, and protein S. Although the signal transduction pathways of TYRO3 have not been evaluated in detail, overexpression and activation of TYRO3 receptor tyrosine kinase have been reported to promote cell proliferation, survival, tumorigenesis, migration, invasion, epithelial-mesenchymal transition, or chemoresistance in several human cancers. Targeting TYRO3 could break the kinase signaling, stimulate antitumor immunity, reduce tumor cell survival, and regain drug sensitivity. To date, there is no specific TYRO3-targeted drug, the effectiveness of targeting TYRO3 in cancer is worthy of further investigations. In this review, we present an update on molecular biology of TYRO3, summarize the development of potential inhibitors of TAM family members, and provide new insights in TYRO3-targeted treatment. Impact statement Cancer is among the leading causes of death worldwide. In 2016, 8.9 million people are estimated to have died from various forms of cancer. The current treatments, including surgery with chemotherapy and/or radiation therapy, are not effective enough to provide full protection from cancer, which highlights the need for developing novel therapy strategies. In this review, we summarize the molecular biology of a unique member of a subfamily of receptor tyrosine kinase, TYRO3 and discuss the new insights in TYRO3-targeted treatment for cancer therapy.

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Mechanisms of acquired resistance to insulin-like growth factor 1 receptor inhibitor in MCF-7 breast cancer cell line

Cited by 14 publications

References 41 publications

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer

Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF-1R/IR Inhibitor in Colon Carcinoma Cells

TYRO3: A potential therapeutic target in cancer

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