NDLI: Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer

Content Provider	Springer Nature Link
Author	Johnson, Rachelle W. Merkel, Alyssa R. Page, Jonathan M. Ruppender, Nazanin S. Guelcher, Scott A. Sterling, Julie A.
Copyright Year	2014
Abstract	Parathyroid hormone-related protein (PTHrP) is an important regulator of bone destruction in bone metastatic tumors. Transforming growth factor-beta (TGF-β) stimulates PTHrP production in part through the transcription factor Gli2, which is regulated independent of the Hedgehog signaling pathway in osteolytic cancer cells. However, inhibition of TGF-β in vivo does not fully inhibit tumor growth in bone or tumor-induced bone destruction, suggesting other pathways are involved. While Wnt signaling regulates Gli2 in development, the role of Wnt signaling in bone metastasis is unknown. Therefore, we investigated whether Wnt signaling regulates Gli2 expression in tumor cells that induce bone destruction. We report here that Wnt activation by β-catenin/T cell factor 4 (TCF4) over-expression or lithium chloride (LiCl) treatment increased Gli2 and PTHrP expression in osteolytic cancer cells. This was mediated through the TCF and Smad binding sites within the Gli2 promoter as determined by promoter mutation studies, suggesting cross-talk between TGF-β and Wnt signaling. Culture of tumor cells on substrates with bone-like rigidity increased Gli2 and PTHrP production, enhanced autocrine Wnt activity and led to an increase in the TCF/Wnt signaling reporter (TOPFlash), enriched β-catenin nuclear accumulation, and elevated Wnt-related genes by PCR-array. Stromal cells serve as an additional paracrine source of Wnt ligands and enhanced Gli2 and PTHrP mRNA levels in MDA-MB-231 and RWGT2 cells in vitro and promoted tumor-induced bone destruction in vivo in a β-catenin/Wnt3a-dependent mechanism. These data indicate that a combination of matrix rigidity and stromal-secreted factors stimulate Gli2 and PTHrP through Wnt signaling in osteolytic breast cancer cells, and there is significant cross-talk between the Wnt and TGF-β signaling pathways. This suggests that the Wnt signaling pathway may be a potential therapeutic target for inhibiting tumor cell response to the bone microenvironment and at the very least should be considered in clinical regimens targeting TGF-β signaling.
Starting Page	945
Ending Page	959
Page Count	15
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	31
Issue Number	8
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-10-31
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Gli PTHrP Osteolysis Wnt Rigidity Bone metastasis Cancer Research Biomedicine general Oncology Hematology Surgical Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer

Genetics of breast cancer bone metastasis: a sequential multistep pattern

Bone metastasis: pathogenesis and therapeutic implications

The Wnt inhibitor dickkopf-1: a link between breast cancer and bone metastases

Silencing of skeletal metastasis-associated genes impairs migration of breast cancer cells and reduces osteolytic bone lesions

β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases

Gene expression profiles and breast cancer metastasis: a genetic perspective

A gene expression signature that defines breast cancer metastases

Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors

Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer

Similar Documents

Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer

Genetics of breast cancer bone metastasis: a sequential multistep pattern

Bone metastasis: pathogenesis and therapeutic implications

The Wnt inhibitor dickkopf-1: a link between breast cancer and bone metastases

Silencing of skeletal metastasis-associated genes impairs migration of breast cancer cells and reduces osteolytic bone lesions

β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases

Gene expression profiles and breast cancer metastasis: a genetic perspective

A gene expression signature that defines breast cancer metastases

Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors

Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer