New paradigms for the Hedgehog signaling network in mammary gland development and breast Cancer

Monkkonen, Teresa; Lewis, Michael T.

doi:10.1016/j.bbcan.2017.06.003

Cited by 36 publications

(27 citation statements)

References 112 publications

(339 reference statements)

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“…Although improper SHH signaling can arise from a variety of mechanisms (see Section 5 above), aberrant SHH signaling in breast cancer tends to occur through Type II ligand-dependent signaling in which tumors cells profusely secrete active SHH ligand into the immediate surrounding area, leading to self-activation or activation of juxtaposed tumor cells [193,252]. This is supported by findings that SHH, PTCH1, and GLI1 mutations are exceedingly rare in breast cancer which argues against the potential involvement of mutational activation of the SHH pathway in breast cancer [253][254][255]. Nevertheless, expression of SHH pathway components correlates with more aggressive breast cancer subtypes and predicts poor overall survival [256,257].…”

Section: Breast Cancermentioning

confidence: 98%

Hedgehog Signaling and Truncated GLI1 in Cancer

Doheny

Manore

Wong

et al. 2020

Cells

121

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The hedgehog (HH) signaling pathway regulates normal cell growth and differentiation. As a consequence of improper control, aberrant HH signaling results in tumorigenesis and supports aggressive phenotypes of human cancers, such as neoplastic transformation, tumor progression, metastasis, and drug resistance. Canonical activation of HH signaling occurs through binding of HH ligands to the transmembrane receptor Patched 1 (PTCH1), which derepresses the transmembrane G protein-coupled receptor Smoothened (SMO). Consequently, the glioma-associated oncogene homolog 1 (GLI1) zinc-finger transcription factors, the terminal effectors of the HH pathway, are released from suppressor of fused (SUFU)-mediated cytoplasmic sequestration, permitting nuclear translocation and activation of target genes. Aberrant activation of this pathway has been implicated in several cancer types, including medulloblastoma, rhabdomyosarcoma, basal cell carcinoma, glioblastoma, and cancers of lung, colon, stomach, pancreas, ovarian, and breast. Therefore, several components of the HH pathway are under investigation for targeted cancer therapy, particularly GLI1 and SMO. GLI1 transcripts are reported to undergo alternative splicing to produce truncated variants: loss-of-function GLI1ΔN and gain-of-function truncated GLI1 (tGLI1). This review covers the biochemical steps necessary for propagation of the HH activating signal and the involvement of aberrant HH signaling in human cancers, with a highlight on the tumor-specific gain-of-function tGLI1 isoform.

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Section: Breast Cancermentioning

confidence: 98%

Hedgehog Signaling and Truncated GLI1 in Cancer

Doheny

Manore

Wong

et al. 2020

Cells

121

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“…[ 13 ] Later, this pathway was also found to be crucial for regulating sexual differentiation, [ 14 ] normal organ development and pathological processes, [ 15 ] especially tumorigenesis. [ 16 ] Based on the study in Drosophila , the Hh pathway was found to mainly consist of the ligand Hh, the receptor patched (PTCH), [ 17 ] the intermediate protein smoothened (SMO), [ 18 ] and the transcription factor cubitus interruptus (Ci). [ 19 ] The process of signal transduction can be described as follows.…”

Section: Hedgehog Pathwaymentioning

confidence: 99%

Where are the theca cells from: the mechanism of theca cells derivation and differentiation

Liu

Qin

et al. 2020

Chinese Medical Journal

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Mammalian follicles are composed of oocytes, granulosa cells, and theca cells. Theca cells form in the secondary follicles, maintaining follicular structural integrity and secreting steroid hormones. Two main sources of theca cells exist: Wilms tumor 1 positive ( Wt1 + ) cells native to the ovary and Gli1 + mesenchymal cells migrated from the mesonephros. Normal folliculogenesis is a process where oocytes, granulosa cells, and theca cells constantly interact with and support each other through autocrine and paracrine mechanisms. The proliferation and differentiation of theca cells are regulated by oocyte-derived factors, including growth development factor 9 and bone morphogenetic protein 15, and granulosa cell-derived factors, including desert hedgehog, Indian hedgehog, kit ligand, insulin-like growth factor 1, as well as hormones such as insulin and growth hormones. Current research on the origin of theca cells is limited. Identifying the origin of theca cells will help us to systematically elaborate the mechanisms of follicular formation and development.

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“…Cancer stem cells contribute to chemotherapy resistance [ 27 , 28 ]. Therefore, Shh signaling pathway molecules could be potential therapeutic targets in breast cancer [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer

Jeng

Sheen

et al. 2018

IJMS

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Overexpression of Sonic Hedgehog signaling (Shh) pathway molecules is associated with invasiveness and recurrence in breast carcinoma. Therefore, inhibition of the Shh pathway downstream molecule Glioma-associated Oncogene Homolog (Gli) was investigated for its ability to reduce progression and invasiveness of patient-derived breast cancer cells and cell lines. Human primary breast cancer T2 cells with high expression of Shh signaling pathway molecules were compared with breast cancer line MDA-MB-231 cells. The therapeutic effects of Gli inhibitors were examined in terms of the cell proliferation, apoptosis, cancer stem cells, cell migration and gene expression. Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells. It reduced Bcl2 expression for cell proliferation and increased Bim expression for apoptosis. In addition, Gli inhibitor HPI-1 decreased significantly the percentages of cancer stem cells in T2 cells. HPI-1 worked more effectively than GANT-58 against breast carcinoma cells. In conclusion, HPI-1 could inhibit cell proliferation, reduce cell invasion and decrease cancer stem cell population in breast cancer cells. To target Gli-1 could be a potential strategy to suppress breast cancer stem cells.

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New paradigms for the Hedgehog signaling network in mammary gland development and breast Cancer

Cited by 36 publications

References 112 publications

Hedgehog Signaling and Truncated GLI1 in Cancer

Hedgehog Signaling and Truncated GLI1 in Cancer

Where are the theca cells from: the mechanism of theca cells derivation and differentiation

Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer

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