Role of c-Src and focal adhesion kinase in progression and metastasis of estrogen receptor-positive breast cancer

Planas-Silva, Maricarmen D.; Bruggeman, Richard; Grenko, Ronald T.; Smith, J. Stanley

doi:10.1016/j.bbrc.2005.12.164

Cited by 81 publications

(72 citation statements)

References 48 publications

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“…Our data combined with that of others (Ito et al, 2002;Diaz et al, 2006;Madan et al, 2006;Planas-Silva et al, 2006), suggests that compared to normal breast epithelium, increased levels of activated c-Src are present in DCIS and invasive breast carcinoma. Activated c-Src levels correlated with HER2 expression, a higher tumour nuclear grade, the presence of comedo necrosis, and higher epithelial proliferative status.…”

Section: Discussionsupporting

confidence: 82%

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

et al. 2006

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Overexpression and/or activity of c-Src non-receptor tyrosine kinase is associated with progression of several human epithelial cancers including breast cancer. c-Src activity in 'pure' ductal carcinoma in situ (DCIS) was measured to assess whether this predicts recurrence and/or correlates with HER2 expression and other clinical parameters. Activated c-Src levels were evaluated in DCIS biopsies from 129 women, with median follow-up at 60 months. High levels of activated c-Src correlated with HER2 positivity, high tumour grade, comedo necrosis and elevated epithelial proliferation. In univariate analysis, high activated c-Src level associated with lower recurrence-free survival at 5 years (P ¼ 0.011). Thus, high c-Src activity may identify a subset of DCIS with high risk of recurrence or progression to invasive cancer where therapeutics targeting c-Src may benefit this patient subset.

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Section: Discussionsupporting

confidence: 82%

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

et al. 2006

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“…Our RT-PCR analysis suggests that these observations might be due to modulation of cyclin-D1 and c-myc, genes which play a central role in the control of cellular proliferation. Such data is not surprising given the reported interplay between Src and cell-cycle-associated genes [54,55]; indeed, it has been recently reported that pharmacological inhibition of Src activity in MCF7 cells results in suppression of both cMyc and cyclinD1 [19]. Our data here demonstrates that prolonged exposure to a Src inhibitor and tamoxifen results in even greater suppression of these elements and interestingly, cell cycle analysis revealed a significant reduction in the numbers of cells in S phase following combination treatment.…”

Section: Discussionsupporting

confidence: 81%

“…However, acquisition of resistance to such therapies frequently arises and, in such cases, the identification of novel targets that promote a resistant phenotype may themselves prove useful targets through which the development of resistance and the associated tumour re-growth and spread may be delayed or prevented. We and others have recently identified a role for Src kinase in acquired endocrine resistance in vitro [11,19], where it may regulate both proliferative and invasive responses in such cells. Data is emerging which reveals Src kinase as a novel tumour target, where its inhibition is effective at suppressing proliferation and/or metastatic events in a wide range of tumour types including CML [30,31], colon tumours [32,33] and pancreatic cancer [34,35].…”

Section: Discussionmentioning

confidence: 99%

“…Significantly, we have recently identified that Src kinase activity is significantly elevated in tamoxifenresistant breast cancer cells, where it promotes an aggressive, invasive phenotype [11]. A role for Src kinase in acquired endocrine resistance has also been suggested by others, where it may contribute to cellular growth via regulation of Cas-mediated EGFR signalling [18] or through interplay with focal adhesion kinase (FAK) [19].…”

Section: Introductionmentioning

confidence: 92%

“…Since prolonged exposure of breast cancer cell lines to antioestrogens ultimately results in acquired resistance [8,9], a process in which activated Src has been implicated [11,18,19], we wished to determine whether inhibition of Src activity alongside tamoxifen treatment would delay or prevent the development of resistance. Chronic exposure of both MCF7 and T47D cells to tamoxifen resulted in the emergence of a resistant phenotype after an initial period of growth suppression, as demonstrated by the ability of these cells to regain their ability to grow in the presence of the antihormone (Fig.…”

Section: Azd0530 and Tamoxifen Together Showed Improved Growth Inhibimentioning

confidence: 99%

See 2 more Smart Citations

Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells

Hiscox

Jordan

Smith

et al. 2008

Breast Cancer Res Treat

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Targeting Src signaling in metastatic bone disease

Araujo¹,

Logothetis²

2008

Intl Journal of Cancer

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Src is a tyrosine kinase involved in the regulation of a range of cellular processes including proliferation, adhesion, motility and survival. In addition, it is a key regulator of bone metabolism. Src has been implicated in the pathogenesis of a number of cancers, and has been found to be overexpressed in breast, prostate, colorectal, pancreatic and nonsmall-cell lung tumors. There is also evidence that aberrant Src signaling may contribute to the increased osteoclastic activity associated with bone metastases. Bone metastases frequently occur in cancer patients with advanced disease. The metastasized cells disrupt normal bone remodeling pathways resulting in the release of growth factors that further promote tumor growth. Thus, a cycle of metastatic bone destruction is initiated, leading to compromised skeletal integrity and substantially reduced quality of life. Because of the role of Src in both cancer development and in bone metabolism, it may provide a therapeutic target for patients with bone metastases. ' 2008 Wiley-Liss, Inc.Key words: Src signaling; tyrosine kinase; bone metastases; osteoclasts Bone involvement in advanced cancerBone metastases are common in several cancers, including breast, prostate, colorectal and lung cancer. In addition, nearly all patients with multiple myeloma experience bone lesions. 1 Although bone resorption by osteoclasts and synthesis of new bone by osteoblasts is tightly regulated in normal bone metabolism, malignant cells dysregulate the bone remodeling process. The chronic presence of bone metastases often results in complete pathologic remodeling of the affected bone compartment.If untreated, bone metastases lead to skeletal complications such as fractures, spinal cord compression and bone pain, all of which may profoundly reduce patients' quality of life. Therefore, early diagnosis and adequate treatment of bone metastases is critically important.Cancer patients are also at risk of bone loss as a result of certain cancer therapies. In premenopausal women, chemotherapy can cause ovarian failure, leading to early menopause and rapid bone loss. 2 Adjuvant endocrine therapies that deplete peripheral sex hormone production can also reduce bone mass. Bone loss is also frequently seen in men receiving androgen-deprivation therapy for prostate cancer, leading to an increased risk of osteoporotic fracture. 3 Molecular biology of Src family kinasesSrc (encoded by the c-src gene) is a nonreceptor tyrosine kinase localized to the cellular membrane, involved in the regulation of a range of cellular processes, including proliferation, adhesion, motility and survival (for a review see Yeatman or Rucci et al. 4,5 ). It is the best-characterized member of the Src family kinases (SFKs), a family of 9 similar proteins that also includes Blk, Fgr, Fyn, Hck, Lck, Lyn, Yes and Yrk. 4,5 SFK members share a unique domain and 3 other domains termed the kinase domain and Src homology (SH) domains SH2 and SH3. The kinase domain phosphorylates tyrosine residues in substrates that bind to the SH...

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Role of c-Src and focal adhesion kinase in progression and metastasis of estrogen receptor-positive breast cancer

Cited by 81 publications

References 48 publications

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells

Targeting Src signaling in metastatic bone disease

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