Common critical pathways in embryogenesis and cancer

Kelleher, Fergal C.; Fennelly, D.; Rafferty, Máirín

doi:10.1080/02841860600602946

Cited by 118 publications

(91 citation statements)

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“…Genes and signaling pathways that normally participate in developmental processes have been shown to also be reactivated in cancer pathogenesis. 36 Thus, BMP4 and other BMP family members have begun to be a common research topic in the cancer field. Interestingly, BMP2 and BMP7 are currently used in the clinic for healing bone fractures.…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Alarmo¹,

Huhtala

Korhonen

et al. 2013

Modern Pathology

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Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor b (TGFb) superfamily and are known to regulate cell proliferation, differentiation and motility, especially during development. BMP4 has an indispensable role in vertebrate development while limited information on BMP4 expression and function exists in adult tissues. Nevertheless, its contribution to cancer development and progression has gained increasing interest in recent years. Functional studies, especially in breast cancer, have implicated BMP4 both in inhibition of cell proliferation and in promotion of cell migration and invasion. To gain an insight into the function of BMP4 in normal and cancer tissues, BMP4 protein expression levels were analyzed by immunohistochemistry in 34 different normal organs/tissues, 34 different tumor types and finally in 486 breast cancer samples where possible associations between BMP4 and clinicopathological parameters were statistically evaluated. In over 20% of normal and malignant tissues, BMP4 was expressed at high level. Strong expression was observed particularly in some normal epithelial cells, such as bladder and stomach, and in squamous cell carcinomas. In breast cancer, strong BMP4 expression was detected in 25% of patients, and was associated with low proliferation index and increased frequency of tumor recurrence. Taken together, BMP4 is expressed in a subset of normal adult tissues and is likely to contribute to tissue homeostasis. However, in tumors, BMP4 expression levels vary considerably, implying diverse roles in different tumor types. This role is biphasic in breast cancer as BMP4 expression is linked to reduced proliferation and increased recurrence, thus corroborating our previous in-vitro functional data.

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Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Alarmo¹,

Huhtala

Korhonen

et al. 2013

Modern Pathology

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“…Thus, evidence that MFB derived from adult rat primary HSC produce Shh has potentially important implications for remodeling of damaged livers. Indeed, the fact that MFB produce a factor that promotes vasculogenesis [15], hematopoiesis [23], and progenitor cell survival [14,41,42] calls into question the wisdom of therapeutic attempts to induce apoptosis in MFB as a strategy for reducing liver fibrosis [48][49][50][51][52]. In other tissues, wound healing is impaired when Shh is inhibited, and accelerates when supplemental Shh is administered [17,21,41,[53][54][55][56].…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence demonstrates that the Hh pathway becomes re-activated in many adult organs during injury, helping to orchestrate wound healing responses [13,14]. For example, Shh promotes vasculogenesis [15,16], cardiac repair [17], neural and skin regeneration [18][19][20][21], bone remodeling [22], and differentiation of hematopoeitic progenitors [23] in adults.…”

Section: Introductionmentioning

confidence: 99%

Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells

Yang

Wang

Mao

et al. 2008

Journal of Hepatology

185

203

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“…2) resembles other developmental signaling pathways, with some unique differences. The Notch protein family consists of four transmembrane receptor proteins that share several key features, including a repeating EGF domain in the extracellular component (Liu et al, 2003;Bray, 2006;Ehebauer et al, 2006;Kelleher et al, 2006). The Notch protein is targeted by the ligands Delta (DLL) and Jagged (JAG), which are transmembrane proteins integrated into the membrane of neighboring cells (Karanu et al, 2000).…”

Section: Notch Pathwaymentioning

confidence: 99%

“…Rapid proliferation and high motility are hallmarks of both development and tumorigenesis; therefore, pathways important for development are probable targets for oncogenic transformations (Wechsler-Reya and Scott, 2001;Vogelstein and Kinzler, 2004;Kelleher et al, 2006;Read et al, 2006). The persistence of neural stem cells into adulthood in the subventricular zone and subgranular zone of the hippocampus (Gage et al, 1995;Eriksson et al, 1998;Morshead and van der Kooy, 2001) also provide a pool of candidate cells for oncogenic transformation because of their extended lifespan and cellular machinery for unlimited growth.…”

Section: Introductionmentioning

confidence: 99%