Hippo vs. Crab: tissue‐specific functions of the mammalian Hippo pathway

Abstract

The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements. In this review, we attempt to systematically summarize results that have been gleaned from detailed in vivo characterizations of these mutants. Our goal is to describe the physiological roles of Hippo signaling in several normal organ systems, as well as to emphasize how disruption of the Hippo pathway, and particularly hyperactivation of YAP1/TAZ, can be oncogenic.

Targeting Cancer Stem Cells: A Strategy for Effective Eradication of Cancer

“…In an attempt to target CSC-regulating effector molecules, we have focused on YAP1, a principal effector of the Hippo signaling pathway that regulates organ growth in normal tissues. Increasing evidence suggests that YAP1 has diverse roles in tumorigenesis and drug resistance [20], and it has been reported to promote malignant features (e.g., cell proliferation, invasion, migration, and anti-apoptosis) [20,128,129,130,131,132] and drug resistance in various cancers, including breast, bladder and lung cancer (Figure 2) [51,52,133]. Recent studies have also shown that YAP1 contributes to the establishment of an immunosuppressive tumor microenvironment [20].…”

Loss of Mob1a/b in mice results in chondrodysplasia due to YAP1/TAZ-TEAD-dependent repression of SOX9

“…We previously reported that Mob1a/b null mutant mice succumb to embryonic lethality at embryonic day (E) 6.5 (Nishio et al, 2013). We have also demonstrated that Mob1a/b loss induces extreme hyperactivation of endogenous YAP1/TAZ, resulting in the most severe phenotypes reported among mice mutated in Hippo core components in various tissues (Nishio et al, 2017). Thus, MOB1A/ B is a crucial hub in the Hippo signaling pathway.…”

The Emerging Link between the Hippo Pathway and Non-coding RNA

“…Moreover, cellular stress signals, [32][33][34][35] as well as metabolism and nutrient signals, [36][37][38][39][40][41] also contribute to the regulation of the Hippo pathway. Disruption of the Hippo pathway causes tissue overgrowth and confers principal features of cancer, [42][43][44] including increased cell proliferation and survival, 45) abnormal cell division, 46,47) and enhanced cell migration. 48,49) In contrast, aberrant activation of the Hippo pathway impairs tissue development, stem cell maintenance, and differentiation.…”